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Intracerebral haemorrhage (ICH) is the deadliest form of stroke, but current treatment options are limited, meaning ICH survivors are often left with life-changing disabilities. The significant unmet clinical need and socioeconomic burden of ICH mean novel regenerative medicine approaches are gaining interest. To facilitate the regeneration of the ICH lesion, injectable biomimetic hydrogels are proposed as both scaffolds for endogenous repair and delivery platforms for pro-regenerative therapies. In this paper, the objective was to explore whether injection of a novel self-assembling peptide hydrogel (SAPH) Alpha2 was feasible, safe and could stimulate brain tissue regeneration, in a collagenase-induced ICH model in rats. Alpha2 was administered intracerebrally at 7 days post ICH and functional outcome measures, histological markers of damage and repair and RNA-sequencing were investigated for up to 8 weeks. The hydrogel Alpha2 was safe, well-tolerated and was retained in the lesion for several weeks, where it allowed infiltration of host cells. The hydrogel had a largely neutral effect on functional outcomes and expression of angiogenic and neurogenic markers but led to increased numbers of proliferating cells. RNAseq and pathway analysis showed that ICH altered genes related to inflammatory and phagocytic pathways, and these changes were also observed after administration of hydrogel. Overall, the results show that the novel hydrogel was safe when injected intracerebrally and had no negative effects on functional outcomes but increased cell proliferation. To elicit a regenerative effect, future studies could use a functionalised hydrogel or combine it with an adjunct therapy., (© 2023. The Author(s).)

There is growing evidence suggesting an increased perception of control is associated with reduced psychological distress among survivors of sexual trauma. The current study advances the extant literature by investigating the association between depressive symptoms, sexual trauma, and an external locus of control or the perception life events are outside one's own control. To do so, we analyze data from the New Family Structures Study, a nationally representative survey of U.S. adults ages 18-39. Results from ordinary least square regression analyses suggest sexual trauma and an external locus of control are associated with significantly greater depressive symptoms and that external control exacerbates the association between sexual trauma and depression. Such findings suggest future research should investigate environmental control for sexual trauma survivors in areas such as prenatal care and the justice system., (© 2024 Springer Publishing Company.)

Context: This research focused on the theoretical investigation of transition metal carbonyls [M(CO) 4 ] coordinated with terminal germanium chalcogenides complexes [M(CO) 3 GeX], where M represents Ni, Pd, and Pt and X represents O, S, Se, and Te labeled 1-15. While the notable complexes M(CO) 4 (where M = Ni, Pd, Pt) numbered 1, 6, and 11 are of significance, substituting one of the CO ligands in 1, 6, and 11 with a GeX ligand (where X = O, S, Se, or Te) result in substituted complexes (2-5, 7-10, and 11-15). Substituting of the CO ligand slightly alters these bond angles. Specifically, the ∠CMC bond angles for [Ni] complexes range from 111.9° to 112.2°, for [Pd] complexes from 111.4° to 111.7°, and for [Pt] complexes from 112.4° to 112.8°. These findings indicate a minor deviation from the tetrahedral geometry due to the influence of the new GeX ligand. Similarly, there is a slight change in the geometry of the metal complexes, where the ∠GeMC angles for [Ni] complexes are between 106.7° and 106.9°, for [Pd] complexes between 107.2° and 107.5°, and for [Pt] complexes between 105.9° and 106.4°. Comparing among the substituted GeX complexes, those containing GeTe exhibit a higher natural bond orbital (NBO) contribution from the Ge atom compared to the M atom. Consequently, based on the above observations, it can be inferred that GeX acts as an effective sigma donor in contrast to carbonyl compounds. Results of energy decomposition analysis (EDA) for the M-CO bond in 1, 6, and 11 and for the M-GeX bond in the other [M(CO) 3 (GeX)] complexes where M = Ni, Pd and Pt. The percentage contribution of ΔE elstat and ΔE orb shows a relatively identical behavior for all ligands in case of each metal complexes., Methods: Density functional theory (DFT) calculations were conducted using the B3LYP/gen/6-31G*/LanL2DZ level of theory to examine transition metal carbonyls [M(CO) 4 ] coordinated with terminal germanium chalcogenides complexes [M(CO) 3 GeX], where M represents Ni, Pd, and Pt, and X represents O, S, Se, and Te labeled 1-15 utilized through the use of Gaussian 09W and GaussView 6.0.16 software packages. Post-processing computational code such as multi-wave function was employed for results analysis and visualization., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Little is known about the association between signet ring cell (SRC) differentiation and response to neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal and junctional adenocarcinoma (EAC). We aimed to assess if SRC differentiation is associated with survival and response to nCT or nCRT in patients with EAC., Methods: Patients who underwent nCT and nCRT followed by surgery for EAC from 2000 until 2016 were identified from two institutional prospectively maintained databases. The pretreatment biopsy report or surgical resection specimen was used to differentiate patients into an SRC or non-SRC group., Results: Overall, 129 (19%) of 689 patients included had SRCs (nCT: n = 64; nCRT: n = 65). The SRC group had a more advanced ypT stage (p = 0.003), a higher number of positive lymph nodes in the resection specimen {median (interquartile range [IQR]) 2 [0-5] vs. 1 [0-3]; p = 0.002} and a higher rate of R1/R2 resections (19.4% vs. 12%; p = 0.026). SRC differentiation was not an independent prognostic factor for overall survival (OS) or disease-free survival (DFS). Following nCT, the SRC group had significantly shorter DFS (median [IQR] 12 [5-50] vs. 23 [8-164]; p = 0.013), but not OS, compared with the non-SRC group. In contrast, no differences according to SRC status for OS or DFS were found in patients who underwent nCRT., Conclusions: SRC differentiation was not independently associated with worse OS in patients with EAC who underwent neoadjuvant therapy and surgery. However, nCRT was associated with greater tumor downstaging and better DFS.

Background: Polypharmacy and potentially inappropriate medications (PIMs) are increasingly common and associated with adverse health effects. However, post-graduate education in polypharmacy and complex medication management for older adults remain limited., Objective: The Initiative to Minimize Pharmaceutical Risk in Older Veterans (IMPROVE) polypharmacy clinic was created to provide a platform for teaching internal medicine (IM) and nurse practitioner (NP) residents about outpatient medication management and deprescribing for older adults. We aimed to assess residents' knowledge of polypharmacy and perceptions of this interprofessional education intervention., Design: A prospective cohort study with an internal comparison group., Participants: IM residents and NP residents; Veterans ≥ 65 years and taking ≥ 10 medications., Intervention: IMPROVE consists of a pre-clinic conference, shared medical appointment, individual appointment, and interprofessional precepting model., Main Measures: We assessed residents' performance on a pre-post knowledge test, residents' qualitative assessment of the educational impact of IMPROVE, and the number and type of medications discontinued or decreased., Key Results: The IMPROVE intervention group (n = 18) had a significantly greater improvement in test scores than the control group (n = 18) (14% ± 15% versus - 1.3% ± 16%) over a period of 6 months (Wilcoxon rank sum, p = 0.019). In focus groups, residents (n = 17) reported perceived improvements in knowledge and skills, noting that the experience changed their practice in other clinical settings. In addition, residents valued the unique interprofessional experience. Veterans (n = 71) had a median of 15 medications (IQR 12-19), and a median of 2 medications (IQR 1-3) was discontinued. Vitamins, supplements, and cardiovascular medications were the most commonly discontinued medications, and cardiovascular medications were the most commonly decreased in dose or frequency., Conclusions: Overall, IMPROVE is an effective model of post-graduate primary care training in complex medication management and deprescribing that improves residents' knowledge and skills, and is perceived by residents to influence their practice outside the program.

Introduction: With modern techniques facilitating limb conservation, amputation for extremity soft-tissue sarcoma (ESTS) is now rare. We sought to determine the indications and outcomes following major amputation for ESTS and whether amputation is prognostic of oncological outcomes in primary disease., Patients and Methods: Patients undergoing major amputations for ESTS from 2004 to 2014 were identified from electronic patient records., Results: The amputation rate in primary localized disease was 4.1%. Overall, 69 patients were identified, including 23 (33.3%) amputations for primary localized disease, 36 (52.2%) amputations for recurrent disease, and 10 (14.5%) amputations for metastatic disease. The local recurrence rate for localized disease at 3 years was 10.4%. Three-year overall survival (OS) was 50.3% following curative amputation, with a median survival of 41 months, and median OS following palliative amputation was 6 months. In the context of primary, localized disease, patients undergoing amputation had a greater proportion of high-grade tumors (69.6% vs. 41.1%; p = 0.009) of greater size (median 16.0 vs. 9.0 cm; p = 0.003) when compared with patients undergoing limb-conserving surgery. The rates of systemic relapse and disease-specific survival were poorer following amputation compared with limb-conserving surgery, however mode of surgery (amputation vs. limb conservation) was only prognostic for OS., Conclusions: Amputation maintains an important role in ESTS and achieves durable local control in those unsuitable for limb-conserving surgery. Survival following amputation in the presence of metastatic disease is poor and should be reserved for patients with significant symptoms.

Background: Isolated limb perfusion (ILP) is indicated in locally advanced melanoma and soft tissue sarcoma of the extremities. This series reports the outcome of patients undergoing ILP with melphalan and tumour necrosis factor α (TNFα) at a single centre., Methods: All patients undergoing ILP from January 2005 to January 2015 were identified from a prospectively maintained database. Those undergoing ILP for in-transit melanoma (ITM) were grouped according to disease burden: low volume and bulky (>2 cm diameter)., Results: A total of 143 perfusions were attempted: 9 and 134 in the upper and lower limbs, respectively. A response was assessable in 129 patients with overall response rates for ITM and sarcoma of 81.8 and 61.1 %, respectively. No difference was found in response rates between low-volume and bulky ITM. Limb salvage rates in these cohorts were 97 and 62 %. Regional toxicity following ILP was minimal with 7 grade III (5.4 %), and 1 grade V (0.8 %) reactions. Median progression-free survival was 11 months in the ITM cohort and 12 months in the sarcoma cohort. In the ITM cohort, complete responses were significantly more durable than partial responses (p = 0.0004). Median disease-specific survival was 21 months in the ITM cohort and was not reached in the sarcoma cohort., Conclusions: TNFα-based ILP is safe and provides excellent palliation of ITM due to rapid progression of systemic disease. It is less effective in sarcoma due to lower initial response rates and a lower incidence of disease dissemination.

Background: Tumours within the retroperitoneum can cause a diagnostic dilemma. A preoperative core needle biopsy often is required to establish a histological diagnosis. Preoperative core needle biopsy for extremity soft-tissue sarcoma is oncologically safe and biopsy site recurrence is extremely rare, attributed to placing the biopsy site within the planned resection field. This study investigates whether preoperative core needle biopsy affects oncological outcomes in retroperitoneal sarcomas., Methods: Patients undergoing resection of intermediate- and high-grade primary retroperitoneal sarcoma from 1990 until 2011 were included. Primary endpoints were immediate biopsy-related complications, local recurrence, and overall survival., Results: A total of 150 patients were included in the analysis. Of these, 90 patients underwent resection after a preoperative biopsy. Median follow-up was 48 months. One patient required hospital admission postbiopsy for an abdominal wall rectus sheath haematoma. No patient developed intra-abdominal complications that required hospitalisation or early operation related to core needle biopsy. No patient developed a biopsy site recurrence. There was no significant increase in either local recurrence (p = 0.101) or overall survival (p = 0.191) after core needle biopsy., Conclusions: Preoperative core needle biopsy for retroperitoneal sarcomas is safe and does not affect oncological outcome.

Background: Little is known about the differences between physicians in training and post training in their willingness to comply with patient requests at the end of life., Objective: To compare the attitudes of attendings and residents regarding a range of patient requests at the end of life, Design: Written, cross-sectional survey, Participants: The cohort included 191 attendings randomly selected across the state of Connecticut and 240 residents from 2 university-affiliated Internal Medicine programs., Main Measures: We surveyed attendings and residents about their willingness to honor the requests of the same decisionally capable elderly patient in five scenarios involving different requests regarding end-of-life treatment., Results: While a large majority of both attendings and residents were willing to comply with each of the requests to withhold intubation (100 % and 94 %, respectively), to extubate (92 % and 77 %), and to give increasingly higher doses of narcotics (94 % and 71 %), a significantly larger proportion of attendings versus residents was willing to comply with each of these requests. Small proportions of attendings and residents were willing to prescribe a lethal amount of sleeping pills (3 % and 5 %, respectively) and to give a lethal injection in its current illegal state (1 % and 4 %). A significantly larger proportion of residents (32 %) compared to attendings (19 %) was willing to give a lethal injection if legal. Adjusting for sociodemographic factors, attending status was independently associated with willingness to extubate [adjusted odds ratio (AOR) = 3.0, 95 % CI = 1.6-5.7] and to give a lethal injection if legal (AOR = 0.5, 95 % CI = 0.3-0.8). The proportion of physicians willing to extubate increased across years since graduation, with the greatest differences occurring across the residency years (69 % to 86 %)., Conclusions and Relevance: Clinical experience was an important determinant of physicians' willingness to perform multiple patient requests at the end of life, with substantial changes in attitudes occurring during residency training. More research is needed to determine whether dedicated clinical exposure for physicians in training influences attitudes.

Background: Unplanned excision of soft tissue sarcoma (STS) accounts for up to 40% of all initial operations for STS and is undertaken when the mass is presumed to be benign. The effect this has on outcome has never been fully established., Methods: Patients with extremity or trunk STS between 2001 and 2005 who were treated by an initial inadvertent operation and then referred immediately to our unit were identified. Outcomes were compared with a control group of patients with STS who were stage-matched and had been treated conventionally by core biopsy and definitive surgery. Endpoints were local recurrence, distant metastases and sarcoma-specific survival., Results: 134 patients who had undergone unplanned excision of STS were identified. One hundred twenty-one underwent further re-excision, and 51 (48%) of these patients had residual tumour identified after surgical re-excision. Two hundred nine stage-matched controls were identified who were treated conventionally. Median follow-up was 51.6 months. Local recurrence rates were considerably higher in the study group (23.8 vs. 11%, p = 0.0016), despite the control group having more stage 3 tumours. When the tumours were matched by stage, an increase in local recurrence was seen across all stages but was most pronounced for stage 3 tumours (37.5 vs. 14.2%, p = 0.005). Metastasis-free and sarcoma-specific survival were also significantly increased for stage 3 tumours., Conclusion: Unplanned initial excision of extremity soft tissue sarcoma may compromise long-term local control of extremity STS despite full further oncological management.

There is concern that visitor-use associated activities, such as bathing, dish washing, wastewater production, and stock animal use near lakes and streams, could cause degradation of water quality in Yosemite National Park. A study was conducted during 2004-2007 to assess patterns in nutrient and Escherichia coli (E. coli) concentrations in the Merced and Tuolumne Rivers and characterize natural background concentrations of nutrients in the park. Results indicated that nutrient and E. coli concentrations were low, even compared to other undeveloped sites in the United States. A multiple linear regression approach was used to model natural background concentrations of nutrients, with basin characteristics as explanatory variables. Modeled nitrogen concentrations increased with elevation, and modeled phosphorus concentrations increased with basin size. Observed concentrations (±uncertainty) were compared to modeled concentrations (±uncertainty) to identify sites that might be impacted by point sources of nutrients, as indicated by large model residuals. Statistically significant differences in observed and modeled concentrations were observed at only a few locations, indicating that most sites were representative of natural background conditions. The empirical modeling approach used in this study can be used to estimate natural background conditions at any point along a study reach in areas minimally impacted by development, and may be useful for setting water-quality standards in many national parks.

Background: Clinicians' discussions about hospice with patients and families are important as a means of communicating end-of-life options., Objective: To identify determinants of clinicians' hospice discussions and the impact of such discussions on hospice use., Design: We interviewed 215 patients age > or = 60 years with advanced cancer, chronic obstructive pulmonary disease (COPD), or heart failure (HF) at least every 4 months for up to 2 years. Participants provided information about their health status and treatment preferences. Clinicians completed a questionnaire every 6 months about their estimates of patient life expectancy and their communication with the patient and family about hospice., Results: In their final survey, clinicians reported discussing hospice with 46% of patients with cancer, compared to 10% with COPD and 7% with HF. Apart from diagnosis of cancer, the factors most strongly associated with hospice discussion were clinicians' estimate of and certainty about patient life expectancy (P < 0.001). However, clinicians were unable to anticipate the deaths of a considerable portion of patients (40%). Although patient unwillingness to undergo minor medical interventions was associated with hospice discussion (P < 0.05), a sizeable portion of clinicians (40%) whose patients reported this characteristic did not have the discussion. Clinicians' discussion of hospice independently increased the likelihood of hospice use (OR = 5.3, 95% CI = 2.3-13)., Conclusions: Clinicians' discussion of hospice for patients with advanced illness, and, ultimately, patients' use of hospice, relies largely on clinician estimates of patient life expectancy and the predictability of disease course. Many clinicians whose patients might benefit from learning about hospice are not having these discussions.

Background: Isolated limb perfusion (ILP) with melphalan is used in the treatment of advanced in-transit melanoma but has no real efficacy for irresectable soft tissue sarcomas arising in the extremities. The addition of tumor necrosis factor (TNF)-alpha may increase response rates for bulky melanoma and for sarcoma, but the potential for major systemic toxicity has limited its use., Methods: Between October 2000 and April 2004, 49 ILPs were performed with melphalan and TNF-alpha. All procedures were performed with continuous leakage monitoring and regional hyperthermia., Results: Forty-nine ILPs were performed for melanoma (n = 30), sarcoma (n = 16), or other tumors (n = 3). The most common indications were widespread in-transit disease for melanoma (n = 29) and irresectable primary disease for sarcoma (n = 9). Complete and partial responses for melanoma were 40% and 37%, and for sarcoma they were 20% and 33%. At a median follow-up of 14 months, 66% of melanoma patients who responded had not experienced local progression, compared with only 37% of sarcoma patients. Progression-free survival was significantly less for patients with sarcoma than melanoma (P = .0476). Four of 16 patients with sarcoma subsequently required amputation for progressive disease., Conclusions: ILP with melphalan and TNF-alpha is a valuable treatment for advanced in-transit melanoma. Significant response rates were also seen in irresectable sarcoma, although the duration of response was limited.

Herbert Snow (1847-1930), a London surgeon with a particular interest in melanoma, was a controversial proponent of anticipatory gland excision well before acceptance of elective lymph node dissections. This article describes the work of Snow within a wider historical context.

Background: We defined the tumor characteristics and prognosis of patients with regional lymph node metastasis (RLNM) from soft tissue sarcoma., Methods: All patients with RLNM from soft tissue sarcoma were identified from the Royal Marsden Hospital Sarcoma Unit prospective database from January 1990., Results: A total of 73 (3.4%) of 2127 patients had RLNM. Fifty-seven patients (78.1%) had RLNM as the first site of spread, and 16 patients (21.9%) presented with RLNM and distant metastasis synchronously. The most common histologies were rhabdomyosarcoma, epithelioid sarcoma, and angiosarcoma. There were 9 T1 and 36 T2 tumors, and tumor size was not available in 28 patients. There were 6 grade 1, 16 grade 2, and 51 grade 3 tumors. Forty-two patients presented with RLNM along with the primary tumor. Of the remaining patients, the median time to development of RLNM from diagnosis of the primary tumor was 13.5 months (95% confidence interval [CI], 1-100 months). The 1-year survival for patients with isolated RLNM was 77.49% (95% CI, 62.99%-86.88%), compared with 36.27% (95% CI, 13.32%-60.04%) for patients who presented with RLNM and distant metastasis (P =.005). The 1-year survival for metachronous and synchronous RLNM was 94.44% (95% CI, 66.64%-99.20%) and 67.54% (95% CI, 47.89%-81.12%), respectively (P =.05)., Conclusions: Lymph node metastasis is rare. Patients who present with isolated RLNM have an improved survival compared with patients who present with regional and distant metastasis at diagnosis. Synchronous RLNM with the primary tumor have a poorer outcome than metachronous RLNM in the absence of distant metastasis.

Background: Primary buttock soft tissue sarcomas in adults are common entities that have been infrequently reported (three clinical series and isolated case reports). We present our experience of buttock sarcomas to better characterize and define the natural history of this condition., Methods: Buttock tumors occurring in adults (>16 years) between January 1990 and January 2002 were identified from the Royal Marsden Hospital's Sarcoma Unit prospective database., Results: Seventy-three buttock sarcomas were evaluated and treated at the Royal Marsden Hospital during this period. Liposarcoma (n = 19), leiomyosarcoma (n = 13), and synovial sarcoma (n = 9) were the most frequent histological types. There were 8 T1 and 61 T2 tumors, and size was not available in 4 patients. Most tumors (n = 64) were located deep to the deep fascia. There were 15 grade 1, 20 grade 2, and 37 grade 3 tumors, and grade was not available in 1 patient. There were 29 tumors contained within the gluteus maximus. Wide excision was performed in 50 patients. Local recurrence and distant metastasis occurred in 15 and 35 patients with a median time of 18 and 8 months, respectively. The rate of local recurrence at 2 years was 20.9% (SE, 6.8%). The 2-year overall and disease-free survival rates were 64.1% (SE, 6.7%) and 48.5% (SE, 6.4%), respectively., Conclusions: Buttock sarcomas present special surgical difficulties because of proximity of the sciatic nerve and the ability of tumors at this site to extend into the pelvis and perineum. Size and grade of the tumor were independent predictors for disease-free and overall survival.

Background: Local recurrence occurs in 10% to 20% of patients with extremity soft tissue sarcomas despite optimal treatment. The association of local recurrence with subsequent survival is controversial and conflicting. There is a need for a staging system to predict outcome in this subset of patients and also to plan optimal treatment, including adjuvant systemic therapy., Methods: Data collected from 110 patients with locally recurrent extremity soft tissue sarcomas were studied. The influence of clinical and pathologic factors on local recurrence, distant metastasis, and disease-specific survival were analyzed by univariate and multivariate techniques., Results: Of the 110 patients who presented with local recurrence, 92 had an isolated local recurrence and 18 had prior or concomitant distant metastases. The 5-year disease-specific survival for all patients was 63% and for those with isolated local recurrence, it was 69%. Histologic grade, malignant fibrous histiocytoma histology, pathologic margins, previous local recurrence, and prior radiotherapy were independent prognostic factors for subsequent local recurrence. Tumor size, histologic grade, and time to local recurrence were independent prognostic factors for distant metastasis and disease-specific survival. A prognostic index was calculated by assigning a score of 1 to 3 for each of the three independent prognostic factors for survival and added to give the prognostic index for each patient. As the prognostic index increased from 3 to 9, there was a progressive increase in the hazard ratios and a corresponding deterioration in survival. The patients were then categorized into three prognostic groups based on the hazard ratios for disease specific survival. The differences in the survival curves were highly statistically significant (P < .0001)., Conclusions: Tumor size, histologic grade, and time to local recurrence are the primary determinants of distant metastases and survival in locally recurrent extremity soft tissue sarcomas. The impact of local recurrence on survival varies considerably. The nature of the local recurrence, rather than its presence per se, is a more useful guide to prognosis. We propose a simple staging system based on size, grade, and time to recurrence that correlates extremely well with prognosis and may serve as a guide to make therapeutic decisions in patients with locally recurrent extremity soft tissue sarcomas.

Background: The biopsy method of choice for soft tissue sarcomas (STS) of the limb and limb girdle is controversial. There have been no randomized controlled trials that compare incision biopsy with Tru-cut biopsy. We present a large series, which includes an analysis of the effectiveness of Tru-cut core biopsy both in a tertiary referral center as well as from many referring hospitals. This is compared with the other methods of biopsy of all soft tissue tumors (STT) referred to this institution., Methods: A retrospective review of all patients who were referred to Royal Marsden Hospital NHS Trust (RMH) from 1989 to 1998., Results: There were 570 patients (576 lesions) identified. Overall Tru-cut biopsy differentiated benign from malignant tumors with a sensitivity of 99.4%, specificity 98.7%, positive predictive value 99.4%, and negative predictive value 98.7% with similar results for RMH and referral hospitals. Tru-cut identified both tumor subtype and grade in approximately 80% of STS. Incision biopsy had similar sensitivity and specificity for differentiating benign from malignant STT as well as subtype of STS but was less accurate for grade assessment. Tumors from patients who were referred after enucleation had a median maximum tumor diameter (MTD) of 4.9 cm, whereas median MTD of tumors diagnosed at referring hospitals by Tru-cut biopsy was 10.6 cm. (P < 0.001)., Conclusion: Tru-cut biopsy is highly sensitive and specific in the diagnosis of STT as well as subtyping and grading of STS. It is equally effective as incision biopsy in all these parameters and has a lesser morbidity. The failure to use Tru-cut biopsy is most likely because of the possibility that STS is not suspected in patients with small tumors even when they are deep to the investing fascia.

Background: Epithelioid sarcoma is a rare high grade soft tissue sarcoma with a known propensity for locoregional recurrence. The literature is limited on other characteristics such as frequency of multifocal disease at presentation, the relationship of presenting size of the primary lesion to prognosis, and the ability of current staging systems to predict prognosis., Methods: Review of the Royal Marsden National Health Service Trust (RMH) experience of 37 cases over 21 years., Results: The mean age was 29 years, with male predominance (2.7:1), and distal limb locations were most common (56%). Five patients presented with multifocal local disease. Median follow-up was 88 months in the 19 patients still alive. The 5- and 10-year actuarial overall survival was 70% and 42%, respectively. Tumors deep to the investing fascia had a worse prognosis than superficial tumors. Regional metastasis events were also associated with significantly worse overall survival. Local recurrence, size of 5 cm or larger, and regional metastasis events were predictive of worse distant metastasis-free survival. Tumor size (<5 cm vs. > or =5 cm), local recurrence events, sex, and site were not significant predictors of survival. The American Joint Committee on Cancer/International Union Against Cancer staging systems and the recently proposed RMH staging system of the Royal Marsden National Health Service Trust provided poor differentiation of prognosis in epithelioid sarcoma. The 5-year actuarial local recurrence rate was 35%. The 5-year actuarial regional nodal metastasis rate was 23%. The actuarial 5-year distant metastasis rate was 40%, with pleuropulmonary metastases the most common site of metastatic disease, and 35% of pleuropulmonary metastases presented with pleural effusion. Median post-distant metastasis survival was 8 months., Conclusions: Epithelioid sarcoma has unusual clinical behavior compared with other high grade soft tissue sarcoma. It has a propensity for multifocal disease at presentation, local recurrence, regional metastasis, and particularly poor prognosis after regional or distant metastatic disease. Size and stage according to the American Joint Committee on Cancer/International Union Against Cancer are unreliable predictors of prognosis.

Background: Myxoid liposarcomas (ML) make up the major subset of liposarcomas, which in most series represent the second or third most common type of soft tissue sarcoma. The tendency for ML to metastasize to other soft tissues (STM) in preference to lung parenchyma has been previously described; however, the natural history of this tumor's behavior is poorly documented. Our intent was to analyze the natural history of ML and further quantify the incidence of STM, concentrating on their significance in terms of survival., Methods: We reviewed the experience at the Royal Marsden Hospital over a 10-year period, documenting the clinicopathological behavior of ML, including the frequency of STM., Results: There were 50 patients, with a median follow-up of 43 months. The actuarial 5-year soft tissue metastasis rate was 31%, and the most common sites of STM were the retroperitoneum, abdominal wall, and abdominal cavity. In those 12 patients who had STM there was a median interval of 23 months after original diagnosis to the time the first metastasis became apparent (range, 0-142 months). Median survival following first metastasis was 35 months; 6 of the 12 patients died between 6 and 50 months. Four patients who had STM remain disease free at 15 to 59 months after their first STM. Any round cell component of the ML was associated with a significantly greater chance of metastatic disease (P = .02). In this series, the overall 5-year and 7-year survival rates were 85% and 68%. Patients with STM had an 11 times greater chance of dying than those who did not., Conclusions: ML usually is an indolent disease, but there is a subset of patients who develop STM and have a significantly worse prognosis. STM can occur years after the initial diagnosis and can be associated with medium-long-term survival after they occur. STM should be managed aggressively because of this.

Background: The establishment of a universally acceptable staging system for soft tissue sarcomas has been hampered by the low incidence, various grading systems, and lack of consensus regarding the value of different prognostic factors. We aimed to evaluate prognostic factors in patients with extremity soft tissue sarcomas and to test the validity of the AJCC/UICC staging system., Methods: Prospectively collected data from 316 previously untreated patients with primary extremity soft tissue sarcomas treated at a single institution between 1989 and 1995 were studied. The influence of clinical and pathological factors on local recurrence, distant metastasis, and disease-specific survival was analyzed by univariate and multivariate techniques., Results: Large tumor size and high histological grade were independent adverse prognostic factors for distant metastasis. Large size, high grade, and positive microscopic surgical margins were independent adverse prognostic factors, and liposarcoma histology was an independent favorable prognostic factor for disease-specific survival. Within each histological grade, there was a progressive decline in survival with increasing tumor size, as reflected by an almost linear increase in hazard ratios. Similarly, there was a progressive fall in survival with increasing grade within each size group (<5 cm, 5 to 10 cm, 10 to 15 cm, and > 15 cm). AJCC staging did not correlate well with prognosis. Survival for intermediate-grade tumors smaller than 5 cm (stage IIA) was better than that for low-grade tumors larger than 5 cm (stage IB) (86% vs. 73%). Survival for high-grade tumors smaller than 5 cm (stage IIIA) was better than that for intermediate-grade tumors larger than 5 cm (stage IIB) (72% vs. 57%). A modified staging system was formulated based on the additive influence of size and grade on the estimated hazard ratios for disease-specific survival, as follows: stage IA, G1T1; stage IB, G1T2 or G2T1; stage IIA, G1T3 or G2T2 or G3T1; stage IIB, G1T4 or G2T3 or G3T2; stage IIIA, G2T4 or G3T3; stage IIIB, G3T4; and stage IV, M1 (G1, G2, G3 = low, intermediate, and high grade; T1, T2, T3, T4 = tumor size < 5 cm, 5-10 cm, 10-15 cm, and > 15 cm, respectively). The 5-year disease-specific survivals of stages IA, IB, IIA, IIB, IIIA, and IIIB were 100%, 83%, 74%, 61%, 39%, and 18%, respectively. The 5-year disease-specific survival for stages I, II, III, and IV were 90%, 67%, 31%, and 6% respectively. The survival difference between each stage was statistically significant (P < .001)., Conclusion: Histological grade and tumor size are equally important determinants of distant metastases and survival. The AJCC/UICC staging system is based primarily on the grade of the tumor, with size used to subgroup each stage. A staging system for extremity soft tissue sarcomas with equal emphasis on grade and size is proposed that correlates extremely well with prognosis.