Management of Locally Recurrent Retroperitoneal Sarcoma in the Adult: An Updated Consensus Approach from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group.

BACKGROUND: Surgery is the mainstay of treatment for retroperitoneal sarcoma (RPS), but local recurrence is common. Biologic behavior and recurrence patterns differ significantly among histologic types of RPS, with implications for management. The Transatlantic Australasian RPS Working Group (TARPSWG) published a consensus approach to primary RPS, and to complement this, one for recurrent RPS in 2016. Since then, additional studies have been published, and collaborative discussion is ongoing to address the clinical challenges of local recurrence in RPS. METHODS: An extensive literature search was performed, and the previous consensus statements for recurrent RPS were updated after review by TARPSWG members. The search included the most common RPS histologic types: liposarcoma, leiomyosarcoma, solitary fibrous tumor, undifferentiated pleomorphic sarcoma, and malignant peripheral nerve sheath tumor. RESULTS: Recurrent RPS management was evaluated from diagnosis to follow-up evaluation. For appropriately selected patients, resection is safe. Nomograms currently are available to help predict outcome after resection. These and other new findings have been combined with expert recommendations to provide 36 statements, each of which is attributed a level of evidence and grade of recommendation. In this updated document, more emphasis is placed on histologic type and clarification of the intent for surgical treatment, either curative or palliative. Overall, the fundamental tenet of optimal care for patients with recurrent RPS remains individualized treatment after multidisciplinary discussion by an experienced team with expertise in RPS. CONCLUSIONS: Updated consensus recommendations are provided to help guide decision-making for treatment of locally recurrent RPS and better selection of patients who would potentially benefit from surgery.

Effects of the short stitch technique for midline abdominal closure on incisional hernia (ESTOIH): randomized clinical trial.

BACKGROUND: Incisional hernia remains a frequent problem after midline laparotomy. This study compared a short stitch to standard loop closure using an ultra-long-term absorbent elastic suture material. METHODS: A prospective, multicentre, parallel-group, double-blind, randomized, controlled superiority trial was designed for the elective setting. Adult patients were randomly assigned by computer-generated sequence to fascial closure using a short stitch (5 to 8 mm every 5 mm, USP 2-0, single thread HR 26 mm needle) or long stitch technique (10 mm every 10 mm, USP 1, double loop, HR 48 mm needle) with a poly-4-hydroxybutyrate-based suture material (Monomax®). Incisional hernia assessed by ultrasound 1 year after surgery was the primary outcome. RESULTS: The trial randomized 425 patients to short (n = 215) or long stitch technique (n = 210) of whom 414 (97.4 per cent) completed 1 year of follow-up. In the short stitch group, the fascia was closed with more stitches (46 (12 s.d.) versus 25 (7 s.d.); P < 0.001) and higher suture-to-wound length ratio (5.3 (2.2 s.d.) versus 4.0 (1.3 s.d.); P < 0.001). At 1 year, seven of 210 (3.3 per cent) patients in the short and 13 of 204 (6.4 per cent) patients in the long stitch group developed incisional hernia (odds ratio 1.97, 95 per cent confidence interval 0.77 to 5.05; P = 0.173). CONCLUSION: The 1-year incisional hernia development was relatively low with clinical but not statistical difference between short and long stitches. Registration number: NCT01965249 (http://www.clinicaltrials.gov).

Defining the role of neoadjuvant systemic therapy in high-risk retroperitoneal sarcoma: A multi-institutional study from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group.

BACKGROUND: In patients with retroperitoneal sarcoma (RPS), the incidence of recurrence after surgery remains high. Novel treatment approaches are needed. This retrospective study evaluated patients with primary, high-risk RPS who received neoadjuvant systemic therapy followed by surgery to 1) determine the frequency and potential predictors of radiologic tumor responses and 2) assess clinical outcomes. METHODS: Clinicopathologic data were collected for eligible patients treated at 13 sarcoma referral centers from 2008 to 2018. Univariable and multivariable logistic models were performed to assess the association between clinical predictors and response. Overall survival (OS) and crude cumulative incidences of local recurrence and distant metastasis were compared. RESULTS: Data on 158 patients were analyzed. A median of 3 cycles of neoadjuvant systemic therapy (interquartile range, 2-4 cycles) were given. The regimens were mostly anthracycline based; however, there was significant heterogeneity. No patients demonstrated a complete response, 37 (23%) demonstrated a partial response (PR), 88 (56%) demonstrated stable disease, and 33 (21%) demonstrated progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Only a higher number of cycles given was positively associated with PR (P = .005). All patients underwent complete resection, regardless of the tumor response. Overall, patients whose tumors demonstrated PD before surgery showed markedly worse OS (P = .005). An indication of a better clinical outcome was seen in specific regimens given for grade 3 dedifferentiated liposarcoma and leiomyosarcoma. CONCLUSIONS: In patients with high-risk RPS, the response to neoadjuvant systemic therapy is fair overall. Disease progression on therapy may be used to predict survival after surgery. Subtype-specific regimens should be further validated.

Management of Primary Retroperitoneal Sarcoma (RPS) in the Adult: An Updated Consensus Approach from the Transatlantic Australasian RPS Working Group.

BACKGROUND: Retroperitoneal soft tissue sarcomas comprise a heterogeneous group of rare tumors of mesenchymal origin that include several well-defined histologic subtypes. In 2015, the Transatlantic Australasian RPS Working Group (TARPSWG) published consensus recommendations for the best management of primary retroperitoneal sarcoma (RPS). Since then, through international collaboration, new evidence and knowledge have been generated, creating the need for an updated consensus document. METHODS: The primary aim of this study was to critically evaluate the current evidence and develop an up-to-date consensus document on the approach to these difficult tumors. The resulting document applies to primary RPS that is non-visceral in origin, with exclusion criteria as previously described. The relevant literature was evaluated and an international group of experts consulted to formulate consensus statements regarding the best management of primary RPS. A level of evidence and grade of recommendation were attributed to each new/updated recommendation. RESULTS: Management of primary RPS was considered from diagnosis to follow-up. This rare and complex malignancy is best managed by an experienced multidisciplinary team in a specialized referral center. The best chance of cure is at the time of primary presentation, and an individualized management plan should be made based on the 29 consensus statements included in this article, which were agreed upon by all of the authors. Whenever possible, patients should be enrolled in prospective trials and studies. CONCLUSIONS: Ongoing international collaboration is critical to expand upon current knowledge and further improve outcomes of patients with RPS. In addition, prospective data collection and participation in multi-institution trials are strongly encouraged.

Morbidity and Outcomes After Distal Pancreatectomy for Primary Retroperitoneal Sarcoma: An Analysis by the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group.

BACKGROUND: Multi-visceral resection often is used in the treatment of retroperitoneal sarcoma (RPS). The morbidity after distal pancreatectomy for primary pancreatic cancer is well-documented, but the outcomes after distal pancreatectomy for primary RPS are not. This study aimed to evaluate morbidity and oncologic outcomes after distal pancreatectomy for primary RPS. METHODS: In this study, 26 sarcoma centers that are members of the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) retrospectively identified consecutive patients who underwent distal pancreatectomy for primary RPS from 2008 to 2017. The outcomes measured were 90-day severe complications (Clavien-Dindo ≥ 3), postoperative pancreatic fistula (POPF) rate, and oncologic outcomes. RESULTS: Between 2008 and 2017, 280 patients underwent distal pancreatectomy for primary RPS. The median tumor size was 25 cm, and the median number of organs resected, including the pancreas, was three. In 96% of the operations, R0/R1 resection was achieved. The 90-day severe complication rate was 40 %. The grades B and C POPF complication rates were respectively 19% and 5% and not associated with worse overall survival. Administration of preoperative radiation and factors to mitigate POPF did not have an impact on the risk for the development of a POPF. The RPS invaded the pancreas in 38% of the patients, and local recurrence was doubled for the patients who had a microscopic, positive pancreas margin (hazard ratio, 2.0; p = 0.042). CONCLUSION: Distal pancreatectomy for primary RPS has acceptable morbidity and oncologic outcomes and is a reasonable approach to facilitate complete tumor resection.

Chances, challenges and outcomes of patients with complex bilobar colorectal liver metastases approached by a combined multimodal therapy with liver resection and local ablative therapy.

BACKGROUND AND OBJECTIVES: In treatment of colorectal liver metastases (CRC-LM), liver surgery combined with systemic therapies and local ablation (LAT) allows improved survival. This study aims at the outcomes of patients with complex bilobar CRC-LM who were intended to undergo multimodal therapy with liver resection and LAT. METHODS: Forty-three CRC-LM patients with recommendation for multimodal treament were extracted from 5878 tumor board decisions between 2014 and 2017. Outcome variables included patient survival, as well as completion of hepatic clearance. Prognostic factors were identified by correlation and a Cox proportional hazards model. RESULTS: Out of 43 patients only 23 achieved complete clearance of CRC-LM. One- and 3-year overall survival of patients with cleared liver disease was 100% and 91.7%, respectively, as compared to 83.8% and 12.1%. Incomplete hepatic clearance was the strongest independent risk factor for overall survival (hazards ratio [HR], 5.86; p = .009). Risk factors for incomplete clearance were higher age (r = .34; p = .026), comorbidities (r = .40; p = .008), major complications (r = .34; p = .024), and prolonged intensive care unit stay (r = .41; p = .017). CONCLUSION: Completion of hepatic clearance is crucial to achieve long-term survival in patients with complex bilobar CRC-LM. Careful patient selection and treatment planning should avoid treatment failure before completing the intended therapy plan when multimodal treatments are planned.

Improved survival after resection of colorectal liver metastases in patients with unresectable lung metastases.

BACKGROUND: Modern systemic therapies considerably improve tumour control and thus open the possibility of new surgical approaches in metastatic colorectal cancer. In this retrospective clinical cohort with a comparison group, we investigated whether liver resection in a combined liver-lung-metastasised stage is justified if pulmonary disease is not resected. METHODS: From 283 patients treated in our institution between 2000 and 2014 for combined colorectal liver- and lung metastases, 35 patients had their pulmonary metastases left in situ while they were eligible for both treatment options: resection versus non-resection of liver metastases. Effectively, 15 of these patients received whereas 20 did not receive a liver resection. In these patients, we compared overall survival and determined risk factors that are associated with poor survival, applying a Cox-Proportional Hazards model. RESULTS: Patients whose liver metastases were resected showed significantly longer median survival compared to patients who did not undergo hepatic surgery (median 2.6 vs 1.5 years, P = 0.0182). The Cox-Proportional Hazards model revealed hepatic metastasectomy to be the strongest determinant of patient survival (HR 5.27; CI: (1.89, 14.65)). CONCLUSION: Our results suggest that surgical removal of liver metastases may be beneficial in selected patients even if concomitant lung metastases cannot be resected.

External Beam Radiation Therapy for Resectable Soft Tissue Sarcoma: A Systematic Review and Meta-Analysis.

PURPOSE: The aim of this study was to evaluate the role of preoperative and postoperative external beam radiation therapy (EBRT) in the treatment of resectable soft tissue sarcomas (STSs) of different tumor locations. METHODS: A systematic literature search was performed to identify studies investigating the effects of EBRT (versus no EBRT) on local recurrence (LR) and overall survival (OS) or comparing different EBRT sequences. Random effects meta-analyses were calculated and presented as cumulative odds ratios (ORs). RESULTS: Sixteen studies (n = 3958 patients) comparing EBRT versus no EBRT, including one randomized controlled trial (RCT) in extremity sarcoma, were analyzed. EBRT appeared to reduce LR in both retroperitoneal tumors (OR 0.47, p < 0.0001) and other locations (OR 0.49, p = 0.001). OS was improved by EBRT in retroperitoneal STSs (OR 0.37, p < 0.0001) but not in other tumor locations. Eleven studies (n = 2140), including one RCT, compared preoperative and postoperative radiotherapy. LR was less frequent following preoperative EBRT in retroperitoneal STSs (OR 0.03, p = 0.02), as well as in other tumor locations (OR 0.67, p = 0.01), while wound complications in extremity sarcoma were more frequent following preoperative EBRT (OR 2.92, p < 0.0001). Several studies included in this meta-analysis bear a high risk of bias and no RCT has been published for retroperitoneal STS. CONCLUSIONS: This meta-analysis supports the use of EBRT for local tumor control in patients with resectable STSs. Based on a small number of non-randomized studies, a positive effect on OS may exist in the subgroup of retroperitoneal STSs.

Association of differential miRNA expression with hepatic vs. peritoneal metastatic spread in colorectal cancer.

BACKGROUND: Though peritoneal carcinomatosis reflects a late stage of colorectal cancer (CRC), only few patients present with synchronous or metachronous liver metastases alongside their peritoneal carcinomatosis. It is hypothesized that this phenomenon may be causally linked to molecular characteristics of the primary CRC. This study used miRNA profiling of primary CRC tissue either metastasized to the liver, to the peritoneum or not metastasized at all thus to identify miRNAs potentially associated with defining the site of metastatic spread in CRC. METHODS: Tissue of the primary tumor stemming from CRC patients diagnosed for either liver metastasis (LM; n = 10) or peritoneal carcinomatosis (PER; n = 10) was analyzed in this study. Advanced CRC cases without metastasis (M0; n = 3) were also included thus to select on those miRNAs most potentially associated with determining metastatic spread in general. miRNA profiling of 754 different miRNAs was performed in each group. MiRNAs being either differentially expressed comparing PER and LM or even triple differentially expressed (PER vs. LM vs. M0) were identified. Differentially expressed miRNAs were further validated by in silico and functional analysis. RESULTS: Comparative analysis identified 41 miRNAs to be differentially expressed comparing primary tumors metastasized to the liver as opposed to those spread to the peritoneum. A set of 31 miRNAs was significantly induced in primary tumors that spread to the peritoneum (PER), while the remaining 10 miRNAs were found to be repressed. Out of these 41 miRNAs a number of 25 miRNAs was triple-differentially expressed (i.e. differentially expressed comparing LM vs. PER vs. M0). The latter underwent in silico analysis. Finally, we demonstrated that miR-31 down-regulated c-MET in DLD-1 colon cancer cells. CONCLUSIONS: This study demonstrates that CRC primary tumors spread to the peritoneum vs. metastasized to the liver display significantly different miRNA profiles. Larger patient cohorts will be needed to validate whether determination of e.g. miR-31 may aid to predict the course of disease and whether this may help to create individualized follow up or treatment protocols. To determine whether certain miRNAs may be involved in regulating the metastatic potential of CRC, functional studies will be essential.

Synchronous colorectal liver metastases: focus on the elderly : An Effectiveness Study from Routine Care.

PURPOSE: The goal of this study was to analyze the use and the effectiveness of both surgery and different chemotherapies in patients with synchronous colorectal liver metastases (CLMs) ≥70 years compared to younger patients. METHODS: Survival was analyzed in 456 patients (24.3% ≥70 years) treated for CLM in a single center using Kaplan-Meier estimation of overall survival (OS), calculation of relative survival as estimate for disease-specific survival, and a Cox regression model. RESULTS: Complete surgical resections were achieved more often in patients aged <70 years (39.2 vs. 28.1%, P = 0.056), and young patients more frequently received irinotecan or platin-based chemotherapies (70.3 vs. 41.6%, P < 0.001). Three-year OS and relative survival of patients ≥70 years were significantly lower compared to younger patients (OS 34.3 vs. 43.5%, P = 0.0114). In a Cox regression model, complete surgical removal of liver metastases was the most effective treatment (HR 0.313, P < 0.001) followed by chemotherapy (irinotecan/platin-based: HR 0.371, 5-FU only: HR 0.673, P < 0.001). Having >5 liver metastases, the presence of extrahepatic metastases, high grading, and a nodal positive primary but not age ≥70 years were associated with an increased risk of death. CONCLUSIONS: Our data support radical resection and highly effective chemotherapy in selected elderly patients with CLM.

Temporary Intraoperative Porto-Caval Shunts in Piggy-Back Liver Transplantation Reduce Intraoperative Blood Loss and Improve Postoperative Transaminases and Renal Function: A Meta-Analysis.

BACKGROUND: The value of temporary intraoperative porto-caval shunts (TPCS) in cava-sparing liver transplantation is discussed controversially. Aim of this meta-analysis was to analyze the impact of temporary intraoperative porto-caval shunts on liver injury, primary non-function, time of surgery, transfusion of blood products and length of hospital stay in cava-sparing liver transplantation. METHODS: A systematic search of MEDLINE/PubMed, EMBASE and PsycINFO retrieved a total of 909 articles, of which six articles were included. The combined effect size and 95 % confidence interval were calculated for each outcome by applying the inverse variance weighting method. Tests for heterogeneity (I 2) were also utilized. RESULTS: Usage of a TPCS was associated with significantly decreased AST values, significantly fewer transfusions of packed red blood cells and improved postoperative renal function. There were no statistically significant differences in primary graft non-function, length of hospital stay or duration of surgery. CONCLUSION: This meta-analysis found that temporary intraoperative porto-caval shunts in cava-sparing liver transplantation reduce blood loss as well as hepatic injury and enhance postoperative renal function without prolonging operative time. Randomized controlled trials investigating the use of temporary intraoperative porto-caval shunts are needed to confirm these findings.

Cancer Stem Cell Markers Are Associated With Distant Hematogenous Liver Metastases But Not With Peritoneal Carcinomatosis in Colorectal Cancer.

Although peritoneal carcinomatosis (PC) displays advanced stage in colorectal cancer (CRC), most patients present without distant metastases. To analyze the expression of cancer stem cell markers immunohistochemistry for CD133, CD44 and ß-catenin was applied to CRC with exclusive PC, exclusive hepatic metastasis and CRC with combined spread. Expression of cancer stem cell markers correlated with hematogeneous metastases to the liver and was absent in patients with exclusive PC. Thus, expression of cancer stem cell markers correlates with different patterns of metastatic spread in CRC. These data indicate that CRC with exclusive PC lack stem cell features needed for distant dissemination.

Effectiveness of regional hyperthermia with chemotherapy for high-risk retroperitoneal and abdominal soft-tissue sarcoma after complete surgical resection: a subgroup analysis of a randomized phase-III multicenter study.

OBJECTIVE: To determine whether regional hyperthermia (RHT) in addition to chemotherapy improves local tumor control after macroscopically complete resection of abdominal or retroperitoneal high-risk sarcomas. BACKGROUND: Within the prospectively randomized EORTC 62961 phase-III trial, RHT and systemic chemotherapy significantly improved local progression-free survival (LPFS) and disease-free survival (DFS) in patients with abdominal and extremity sarcomas. That trial included macroscopically complete and R2 resections. METHODS: A subgroup analysis of the EORTC trial was performed and long-term survival determined. From 341 patients, 149 (median age 52 years, 18-69) were identified with macroscopic complete resection (R0, R1) of abdominal and retroperitoneal soft-tissue sarcomas (median diameter 10 cm, G2 48.3%, G3 51.7%). Seventy-six patients were treated with EIA (etoposide, ifosfamide, doxorubicin)+RHT (≥5 cycles: 69.7%) versus 73 patients receiving EIA alone (≥5 cycles: 52.1%, P=0.027). LPFS and DFS as well as overall survival were determined. RESULTS: RHT and systemic chemotherapy significantly improved LPFS (56% vs 45% after 5 years, P=0.044) and DFS (34% vs 27% after 5 years, P=0.040). Overall survival was not significantly improved in the RHT group (57% vs 55% after 5 years, P=0.82). Perioperative morbidity and mortality were not significantly different between groups. CONCLUSIONS: In patients with macroscopically complete tumor resection, RHT in addition to chemotherapy resulted in significantly improved local tumor control and DFS without increasing surgical complications. Within a multimodal therapeutic concept for abdominal and retroperitoneal high-risk sarcomas, RHT is a treatment option beside radical surgery and should be further evaluated in future trials.

Complete pathological response to neoadjuvant pemetrexed/cisplatin in combination with regional hyperthermia in a patient with sarcomatoid peritoneal mesothelioma.

Diffuse malignant peritoneal mesothelioma (DMPM) is a rare disease. Although most patients eligible for surgery undergo cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy, the role of perioperative systemic chemotherapy still remains undefined. Here we report the case of a 52-year-old female patient with advanced sarcomatoid DMPM. After five cycles of systemic pemetrexed and cisplatin, along with two cycles of regional hyperthermia, tumor resection with histomorphological examination showed a complete pathological response. We therefore conclude that there is a subgroup of DMPM patients that might benefit from systemic neoadjuvant chemotherapy with pemetrexed and cisplatin.

Dehydroepiandrosterone modulates T-cell response after major abdominal surgery.

BACKGROUND: The immune balance controlled by T-helper (Th)1 and Th2 cells is critical in protecting the host from pathogenic invasion, and its imbalance may increase susceptibility to infection in patients undergoing major surgery. The differentiation of naive T cells to Th1 and Th2 cells is largely driven by cytokines. In addition, steroid hormones have been shown to affect Th1/Th2 balance, particularly in autoimmune diseases. The regulation of Th1/Th2 balance in patients undergoing surgery and its potential clinical relevance remain unclear. MATERIALS AND METHODS: Blood samples were obtained from patients both before and 2 h after major abdominal surgery. Peripheral blood mononuclear cells were isolated and cultured in wells coated with either anti-CD3 (direct T-cell stimulation) or phytohemagglutinin (PHA) (indirect T-cell stimulation), with or without 10(-5) M dehydroepiandrosterone (DHEA). The release of interleukin (IL)-2, interferon gamma, and IL-10 was measured by an enzyme-linked immunosorbent assay, and the expression of CD4, CD8, and CD69 was determined by flow cytometry. RESULTS: DHEA decreased the release of IL-2 and IL-10 in directly (anti-CD3) and indirectly (PHA)-stimulated T cells from postoperative samples, whereas the release of interferon gamma in PHA-stimulated T cells was not affected. The distribution of CD4/CD8 was not significantly different after surgery or DHEA. DHEA was associated with a decrease in the expression of the activation marker CD69 on CD4(+) T cells, whereas the activation of CD8(+) T cells remained unchanged. CONCLUSIONS: These results demonstrate that DHEA plays a critical role in controlling Th1/Th2 balance in the immediate postoperative period. Attenuation of both the Th1 and Th2 responses has been suggested to have immunoprotective effects. The role of DHEA in the regulation of Th1/Th2 balance in patients undergoing major abdominal surgery may, therefore, also be of significant clinical relevance and warrants further investigation.

Quality of life in peritoneal carcinomatosis: a prospective study in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC).

BACKGROUND/AIMS: Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion (HIPEC) can improve survival in selected patients with peritoneal carcinomatosis, but bear a significant risk of perioperative morbidity. The aim of this study was to prospectively evaluate the quality of life (QoL) following cytoreduction and HIPEC. METHODS: In this study including 40 patients (65% females) with different primary tumors, the EORTC QLQ-C30 questionnaire was applied prior to CS and HIPEC as well as 3, 9, and 18 months postoperatively. RESULTS: Global health status was not impaired significantly following HIPEC. Scales and symptom scores that deteriorated 3 months postoperatively (p < 0.05), that is, physical, role, and social functions as well as fatigue, pain, dyspnea, insomnia, and diarrhea, all returned to preoperative values within 9 months. CONCLUSIONS: Following cytoreductive surgery and HIPEC, QoL returns to preoperative levels within 9 months. Selected patients that are likely to benefit oncologically from HIPEC should not be denied this option for fear of reduced postoperative QoL.

Refusal of Adjuvant Therapies and Its Impact on Local Control and Survival in Patients with Bone and Soft Tissue Sarcomas of the Extremities and Trunk.

BACKGROUND: In soft tissue or bone sarcomas, multimodal therapeutic concepts represent the standard of care. Some patients reject the therapeutic recommendations due to several reasons. The aim of this study was to assess the impact of that rejection on both prognosis and local recurrence. METHODS: Between 2012 and 2019, a total of 828 sarcoma patients were surgically treated. Chemotherapy was scheduled as a neoadjuvant, and adjuvant multi-agent therapy was performed following recommendations from an interdisciplinary tumor board. Radiotherapy, if deemed appropriate, was administered either in a neoadjuvant or an adjuvant manner. The recommended type of therapy, patient compliance, and the reasons for refusal were documented. Follow-ups included local recurrences, diagnosis of metastatic disease, and patient mortality. RESULTS: Radiotherapy was recommended in 407 (49%) patients. A total of 40 (10%) individuals did not receive radiation. A reduction in overall survival and local recurrence-free survival was evident in those patients who declined radiotherapy. Chemotherapy was advised for 334 (40%) patients, 250 (75%) of whom did receive all recommended cycles. A total of 25 (7%) individuals did receive a partial course while 59 (18%) did not receive any recommended chemotherapy. Overall survival and local recurrence-free survival were reduced in patients refusing chemotherapy. Overall survival was worst for the group of patients who received no chemotherapy due to medical reasons. Refusing chemotherapy for non-medical reasons was seen in 8.8% of patients, and refusal of radiotherapy for non-medical reasons was seen in 4.7% of patients. CONCLUSIONS: Divergence from the advised treatment modalities significantly impacted overall survival and local recurrence-free survival across both treatment modalities. There is an imperative need for enhanced physician-patient communication. Reducing treatment times, as achieved with hypofractionated radiotherapy and with therapy in a high-volume sarcoma center, might also have a positive effect on complying with the treatment recommendations.

Effect of Surgery on Postoperative Levels of the Gut Homeostasis-Regulating Enzyme Intestinal Alkaline Phosphatase.

BACKGROUND: Intestinal homeostasis is a crucial factor for complication-free short- and long-term postoperative recovery. The brush border enzyme intestinal alkaline phosphatase (IAP) is an important regulator of gut barrier function and intestinal homeostasis and prevents endotoxemia by detoxifying lipopolysaccharides (LPSs). As IAP is predominantly secreted by enterocytes in the duodenum, we hypothesized that pancreaticoduodenectomy (PD) leads to a significantly stronger decrease in IAP than other major abdominal surgery. STUDY DESIGN: Pre- and postoperative blood, stool, and intestinal samples were collected from patients undergoing PD, as well as other major surgical procedures without duodenectomy. The samples were analyzed using enzyme histochemistry, the para -nitrophenyl phosphate method for IAP, and the limulus amebocyte lysate assay for LPS. RESULTS: Overall, 88 patients were prospectively enrolled in the study. Fecal IAP activity negatively correlated with serum LPS (r = -0.3603, p = 0.0006). PD led to a significant decline in IAP compared to preoperative baseline levels (p < 0.0001). The decline in IAP correlated with the length of proximal small intestinal resection (r = 0.4271, p = 0.0034). Compared to controls, PD was associated with a much more pronounced reduction in IAP-also after adjusting for surgical trauma (operative time, blood loss; r = 0.4598, p = 0.0086). Simultaneously, PD triggered a clearly more prominent increase in serum LPS compared to controls (p = 0.0001). Increased postoperative LPS was associated with an elongated hospitalization (r = 0.7534, p = 0.0062) and more prominent in pancreatic cancer (p = 0.0009). CONCLUSIONS: Based upon the functional roles for IAP, supplementation with exogenous IAP might be a new treatment option to improve short- and long-term outcome after PD.