How-we-do-it: the repair of postoperative ventral hernias after a Mercedes abdominal incision.

PURPOSE: To describe the abdominal wall reconstruction technique with an Ultrapro mesh and outcome for the repair of postoperative ventral hernias after the use of a Mercedes incision during the initial abdominal operation. METHOD: A retrospective review of all the patients undergoing elective postoperative ventral hernia repair between 2013 and 2019. The cohort of these patients that had an initial Mercedes incision was used for this study. RESULTS: Fourteen patients met the criteria for this study. Thirteen of the patients were transplant patients (10 liver transplant and 3 combined pancreas and kidney transplant), and one patient was after a hepatectomy. Fifty-seven percent of these hernias were multiple defects. All the patients underwent the same repair of a modified Rives-Stoppa, transversus abdominis release, and a bilateral transverse plication. A partially absorbable Ultrapro mesh was used for all the patients, with two of the patients needing an additional Symbotex mesh in order to bridge a portion of the posterior fascia. There were 6 minor early postoperative complications (hematoma, superficial wound infection, and seroma) that did not require reoperation. Two patients were readmitted for observation of a wound hematoma, and two patients (14.2%) had recurrence during the follow-up period. The average length of hospitalization was 5.6 days. CONCLUSION: This technique, with the use of an Ultrapro mesh, was found to be safe and effective for the repair of a postoperative ventral hernia due to an initial Mercedes incision.

Number of evaluated lymph nodes and positive lymph nodes, lymph node ratio, and log odds evaluation in early-stage pancreatic ductal adenocarcinoma: numerology or valid indicators of patient outcome?

BACKGROUND: We evaluated the prognostic significance and universal validity of the total number of evaluated lymph nodes (ELN), number of positive lymph nodes (PLN), lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) in a relatively large and homogenous cohort of surgically treated pancreatic ductal adenocarcinoma (PDAC) patients. METHODS: Prospectively accrued data were retrospectively analyzed for 282 PDAC patients who had pancreaticoduodenectomy (PD) at our institution. Long-term survival was analyzed according to the ELN, PLN, LNR, and LODDS. RESULTS: Of these patients, 168 patients (59.5 %) had LN metastasis (N1). Mean ELN and PLN were 13.5 and 1.6, respectively. LN positivity correlated with a greater number of evaluated lymph nodes; positive lymph nodes were identified in 61.4 % of the patients with ELN ≥ 13 compared with 44.9 % of the patients with ELN < 13 (p = 0.014). Median overall survival (OS) and 5-year OS rate were higher in N0 than in N1 patients, 22.4 vs. 18.7 months and 35 vs. 11 %, respectively (p = 0.008). Mean LNR was 0.12; 91 patients (54.1 %) had LNR < 0.3. Among the N1 patients, median OS was comparable in those with LNR ≥ 0.3 vs. LNR < 0.3 (16.7 vs. 14.1 months, p = 0.950). Neither LODDS nor various ELN and PLN cutoff values provided more discriminative information within the group of N1 patients. CONCLUSIONS: Our data confirms that lymph node positivity strongly reflects PDAC biology and thus patient outcome. While a higher number of evaluated lymph nodes may provide a more accurate nodal staging, it does not have any prognostic value among N1 patients. Similarly, PLN, LNR, and LODDS had limited prognostic relevance.

Molecular prognosticators of complex karyotype soft tissue sarcoma outcome: a tissue microarray-based study.

BACKGROUND: Molecular markers are currently being utilized as sensitive prognosticators of cancer patient outcome. We sought to identify prognostic biomarkers for complex karyotype soft tissue sarcoma (STS). MATERIALS AND METHODS: A large (n = 205) clinically annotated tissue microarray (TMA) was constructed and immunostained for several tumor-related markers. Staining was scored via an automated Ariol image analysis system; data were statistically analyzed to evaluate the correlation of clinicopathological and molecular variables with overall survival (OS) and local recurrence. RESULTS: Multivariable analysis identified older age [hazard ratio (HR) 1.62, P < 0.0001], nonextremity location (HR 2.95, P = 0.001), high tumor grade (HR 2.5, P = 0.02), and increased matrix metalloproteinase (MMP) 2 expression (HR 1.74, P = 0.04) as predictors for poor OS. Similarly, older age (HR 1.51, P = 0.008), nonextremity location (HR 4.09, P = 0.001), and increased MMP2 expression (HR 6.28, P = 0.006) were all found to correlate with shorter local recurrence-free interval. High nuclear p53 expression was associated with shorter STS local recurrence-free interval, with a trend toward significance. CONCLUSIONS: Data presented indicate that a clinically annotated TMA can be utilized to identify STS-related prognostic markers. Specifically, MMP2 and nuclear p53 should be further evaluated for their potential inclusion in complex karyotype STS staging systems.

Postoperative nomogram for survival of patients with retroperitoneal sarcoma treated with curative intent.

BACKGROUND: Current American Joint Committee on Cancer retroperitoneal sarcoma (RPS) staging is not representative of patients with RPS specifically and has limited discriminative power. Our objective was to develop a RPS disease-specific nomogram capable of stratifying patients based on probability of overall survival (OS) after resection. PATIENTS AND METHODS: In all, 1118 RPS patients were evaluated at our institution (1996-2006). Patients with resectable, nonmetastatic disease were selected (n = 343) and baseline, treatment and outcome variables were retrieved. A nomogram was created and its performance was evaluated by calculating its discrimination (concordance index) and calibration and by subsequent internal validation. RESULTS: Median follow-up and OS were 50 and 59 months, respectively. Independent predictors of OS were included in the nomogram: age (> or = 65), tumor size (> or = 15 cm), type of presentation (primary versus recurrent), multifocality, completeness of resection and histology. The concordance index was 0.73 [95% confidence interval (CI) 0.71-0.75] and the calibration was excellent, with all observed outcomes within the 95% CI of each predicted survival probability. CONCLUSIONS: A RPS-specific postoperative nomogram was developed. It improves RPS staging by allowing a more dynamic and robust disease-specific risk stratification. This prognostic tool can help in patient counseling and for selection of high-risk patients that may benefit from adjuvant therapies or inclusion into clinical trials.

Outcome of locally recurrent and metastatic angiosarcoma.

BACKGROUND: Angiosarcoma (AS) is a rare soft tissue sarcoma with an enhanced propensity for local and systemic failure. The outcome of locally recurrent and metastatic AS treated at a single institution was evaluated. METHODS: Medical records of AS patients treated for local recurrence and distant metastasis (1993-2008) were retrospectively reviewed. Univariable and multivariable analyses were performed to identify prognosticators. RESULTS: Forty-four patients were treated for locally recurrent AS; the majority (59%) were 5 cm as the only independent adverse prognosticator of recurrent AS-specific survival [hazard ratio (HR): 3.26, P = 0.04]. Ninety-nine patients were treated for metastatic AS; 73% had multiple metastatic sites; the lung was the most common site (36%). Chemotherapy, mainly doxorubicin- and/or paclitaxel-based regimens, were administered to 95 patients (96%). Radiotherapy was utilized in 25% cases; 16% of patients underwent curative-intent surgery. Median DSS was 10 months (95% CI: 7.9-12 months). Isolated lymph node metastasis versus hematogenic spread was the only statistically significant favorable prognostic factor identified (HR: 0.29, P = 0.01). CONCLUSION: Locally recurrent AS is often treatable; complete resection can potentially prolong survival. In contrast, metastatic patients have a grave prognosis; however, patients with isolated lymphatic spread and possibly those treated with taxol-based chemotherapeutic regimens have a favorable outcome.

Complete soft tissue sarcoma resection is a viable treatment option for select elderly patients.

BACKGROUND: Decreased performance status, comorbidities, and disease natural history may erode enthusiasm for soft tissue sarcoma (STS) resection in elderly patients. Consequently, we evaluated the outcome of elderly patients amenable to complete surgical resection treated at a single institution. METHODS: Prospectively accrued data were used to identify patients with primary STS age >or=65 years (n = 325) who underwent complete macroscopic resection at our institution (1996-2007). Univariable and multivariable analyses were performed to identify prognostic factors. RESULTS: Median age at presentation was 72 years; 179 patients (55.1%) had associated comorbidities with an ASA score of >or=3. Extremity was the most common site (57.1%; n = 186), undifferentiated pleomorphic sarcoma the most common histology (60.4%; n = 197); 232 (71.2%) were high grade, 222 (68.3%) were >5 cm. Thirty-day postoperative mortality was 0.9% (n = 3); overall complication rate was 30.7% (n = 100), and mean postoperative hospital stay was 9 days (range, 1-84). Estimated median survival was 96 months, 5-year disease-specific survival (DSS) was 63%. Multivariable analysis identified age >or=75 year (HR = 2.03), tumor size: 5-15 vs <5 cm (HR = 3.54), or >15 vs <5 cm (HR = 10.33), and high-grade (HR = 5.53) as significant independent adverse prognostic factors. Compared with patients aged 65-74 years, older patients had more high grade tumors (P = .04), received chemotherapy less often (P < .0001), developed different patterns of recurrence (P < .05), and exhibited a shorter median survival (70 months; P = .05). CONCLUSIONS: Properly selected elderly patients can safely undergo extensive STS resections. Until more effective therapies become available, surgery in the elderly is indicated and remains the best means for STS control.

Resectable well-differentiated versus dedifferentiated liposarcomas: two different diseases possibly requiring different treatment approaches.

BACKGROUND: Division of retroperitoneal liposarcoma (RPLS) into well-differentiated (WD) and dedifferentiated (DD) subtypes is established; however, WD and DD are usually treated similarly. We hypothesized that WD and DD have distinct biological behaviors mandating different treatments. METHODS: A prospective sarcoma database identified all primary/recurrent RPLS treated between 1996 and 2007: 77 DD (52%) and 58 WD (39.2%) patients were analyzed for recurrence rate, recurrence free survival (RFS), and overall survival (OS). RESULTS: At presentation, WD were mostly primary whereas DD were mostly recurrent (75.9% versus 58.4%; p = 0.04). A significant proportion of DD (37.7%) received chemotherapy compared to WD (1.7%; p < 0.0001). Multivisceral resection was more common in DD versus WD (45.5% versus 31%; p = 0.01). Gross total resection rates were equivalent (WD: 86.2%; DD: 85.7%). Overall and local recurrence were higher in DD versus WD (82.2% versus 50% and 71.2% versus 46.3%; p < 0.0001). Only 3.7% WD recurred as high grade metastatic disease. Median time to recurrence was 55.5 months in WD versus 13.5 months in DD (p < 0.0001). RFS and OS (1, 2, and 5 year) were higher in WD than DD (80.3% versus 55.9%; 65.1% versus 34.1%; 41.9% versus 7.8%; p < 0.0001) and (98% versus 88.1%; 95.6% versus 71.9%; 92.1% versus 36.5%; p < 0.0001) respectively. CONCLUSION: WD and DD have distinct biological behaviors. Gross total resection is achievable in most WD; unlike DD, high-grade recurrence is uncommon. Treatment should therefore reflect these biologic differences by maximizing survivorship while avoiding unnecessarily extensive multivisceral resection. SYNOPSIS: The biological behaviors of well-differentiated and dedifferentiated liposarcomas differ significantly. This article presents outcomes of two different surgical approaches that were implemented at the UTMDACC, treating these tumors as different disease entities.

New perspectives for staging and prognosis in soft tissue sarcoma.

BACKGROUND: Data suggest that the current American Joint Committee on Cancer (AJCC) soft tissue sarcoma (STS) staging criteria merit further evaluation. We sought to identify and validate factors as enhanced descriptors of STS clinical behavior. METHODS: Prospectively accrued data were analyzed for 1,091 AJCC stage I to III primary STS patients who had complete macroscopic resection at our institution from 1996 to 2007. Study factors were examined by univariable and multivariable analyses to identify independent prognostic factors for disease related mortality and overall survival (OS). RESULTS: In contrast to the current AJCC STS staging system, which stratifies size into T1 (5 cm) groups, we demonstrated three distinct cohorts (P < 0.0001): T1 (15 cm; OS 52%). A two-category system of histologic grade was demonstrably as informative as the current four histologic grade AJCC system. A multivariable Cox proportional hazard model identified tumor size (5 to 15 cm vs. 15 cm vs.

Solid pseudopapillary neoplasm of the pancreas: Management and long-term outcome.

BACKGROUND: Solid pseudopapillary neoplasm (SPN) of pancreas is a rare pancreatic neoplasm with a low metastatic potential. Our aim was to study the clinical-pathological characteristics, and long-term outcome of this tumor. MATERIALS: Rretrospective single center study of patients operated for SPN of pancreas. Clinical and pathological data were collected. RESULTS: From 1995 to 2016, 1320 patients underwent pancreatic resection. SPN was confirmed in 32 cases (2.46%), including 29 (90.6%) female and three (9.4%) male, with a mean age of 28.4 ± 12.2 years. SPN was the most common pathology among female patients under age of 40 (72.4%). Abdominal pain was the most frequent presenting symptom (48%), whereas none of the patients presented with jaundice. Mean tumor diameter was 5.9 cm (range, 0.9-14 cm). All patients underwent margin-negative surgical resection. Two patients demonstrated gross malignant features, including liver metastases at presentation (n = 1), and adjacent organ and vascular invasion (n = 1). Microscopic malignant features were present in thirteen patients (40.6%). Recurrence occurred in the retroperitoneal lymph nodes (n = 1, 7 years post resection) and in the liver (n = 2, 1 and 5 years post resection). Mean follow-up was 49.2 months (range, 1-228 months). Five and 10-year disease-free survival was 96.5% and 89.6% respectively. CONCLUSIONS: SPNs are low-grade tumors with a good prognosis. Margin-negative surgical resection is curative in most patients. However, almost 15% of patients demonstrate malignant features including invasion of adjacent organs or metastatic disease. Patients with malignant disease are still expected to have long survival, and aggressive surgical approach is advocated.

Vimentin is a novel AKT1 target mediating motility and invasion.

The PI3K/AKT signaling pathway is aberrant in a wide variety of cancers. Downstream effectors of AKT are involved in survival, growth and metabolic-related pathways. In contrast, contradictory data relating to AKT effects on cell motility and invasion, crucial prometastatic processes, have been reported pointing to a potential cell type and isoform type-specific AKT-driven function. By implication, study of AKT signaling should optimally be conducted in an appropriate intracellular environment. Prognosis in soft-tissue sarcoma (STS), the aggressive malignancies of mesenchymal origin, is poor, reflecting our modest ability to control metastasis, an effort hampered by lack of insight into molecular mechanisms driving STS progression and dissemination. We examined the impact of the cancer progression-relevant AKT pathway on the mesenchymal tumor cell internal milieu. We demonstrate that AKT1 activation induces STS cell motility and invasiveness at least partially through a novel interaction with the intermediate filament vimentin (Vim). The binding of AKT (tail region) to Vim (head region) results in Vim Ser39 phosphorylation enhancing the ability of Vim to induce motility and invasion while protecting Vim from caspase-induced proteolysis. Moreover, vimentin phosphorylation was shown to enhance tumor and metastasis growth in vivo. Insights into this mesenchymal-related molecular mechanism may facilitate the development of critically lacking therapeutic options for these devastating malignancies.

Efficacy of high vs low dose TNF-isolated limb perfusion for locally advanced soft tissue sarcoma.

AIMS: The administration of a high dose of rTNF-alpha (3-4 mg) and Melphalan via isolated limb perfusion (ILP) for patients with locally advanced limb STS was shown to be effective. Reports that a low dose of TNF (1mg) is as effective, led to the adoption of the low dose regimen as the treatment of choice. The purpose of this study was to compare two groups of patients with locally advanced limb STS, that was treated with high and low dose TNF-ILP, in terms of limb preservation. METHODS: Retrospective study of 41 patients who underwent ILP, with "high dose" (HD) and "low dose" (LD) TNF. ILP/TNF was performed on candidates to either amputation or significantly mutilating surgery without this treatment. In both groups, all patients, with the exception of three in each group, underwent resection of the residual tumor or tumor bed or limb 8-12 weeks after the procedure. RESULTS: In the HD group, marked tumor softening occurred within 48 h, and in tumors protruding through the skin, hemorrhagic necrosis was evident within 24h. The overall response rate was 65.2%. Five patients achieved a CR and 10 had a PR; in five of these patients >90% necrosis of the tumor occurred. In eight patients, only minimal regression was observed (stabilization of disease). The rate of limb sparing was 69.5%. In the LD group, the overall response rate was 30.7%. CR was achieved in one patient. PR was observed in two. Two patients were lost to follow up. Of the remaining 15 patients, limb preservation was achieved in 53.3%. CONCLUSION: Despite the retrospective comparison and possible selection bias, it is possible to raise the concern that at least some patients may benefit from a higher TNF dose perfusion in ILP for advanced limb STS.

Wound infection after ileostomy closure: a prospective randomized study comparing primary vs. delayed primary closure techniques.

BACKGROUND: Closure of ileostomy is considered a contaminated operation. The infection rate of the stoma wound is > or = 30%. Several ileostomy-closure techniques intended to reduce the high rate of infection have been described in the literature. Among them, delayed primary closure of the stoma wound is a commonly used method that was reported to reduce the infection rate according to several retrospective studies. We therefore conducted the first prospective randomized trial comparing primary with delayed primary closure of a stoma wound. METHODS: During 2003, 40 patients were admitted to our ward for closure of ileostomy. The ileostomies were taken down by the same team using the same surgical technique except for the technique of wound closure. We randomly divided the patients into two groups. In Group 1 (n = 20), the wound was left open for delayed primary closure and not closed until postoperative day 4. In Group 2, the wound was primarily closed at the end of the procedure. RESULTS: The total wound infection rate was relatively low (15%). Infection occurred more frequently (4 cases, 20%) in Group 1 than in Group 2 (2 cases, 10%). The length of hospital stay was similar for both groups. CONCLUSIONS: In this first prospective comparison of two techniques during ileostomy take down, primary closure unexpectedly produced less wound infection than delayed primary closure.