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Introduction The empty pelvis syndrome is a significant source of morbidity following pelvic exenteration surgery. It remains poorly defined with research in this field being heterogeneous and of low quality. Furthermore, there has been minimal engagement with patient representatives following pelvic exenteration with respect to the empty pelvic syndrome. ‘PelvEx—Beating the empty pelvis syndrome’ aims to engage both patient representatives and healthcare professionals to achieve an international consensus on a core outcome set, pathophysiology and mitigation of the empty pelvis syndrome.Methods and analysis A modified-Delphi approach will be followed with a three-stage study design. First, statements will be longlisted using a recent systematic review, healthcare professional event, patient and public engagement, and Delphi piloting. Second, statements will be shortlisted using up to three rounds of online modified Delphi. Third, statements will be confirmed and instruments for measurable statements selected using a virtual patient-representative consensus meeting, and finally a face-to-face healthcare professional consensus meeting.Ethics and dissemination The University of Southampton Faculty of Medicine ethics committee has approved this protocol, which is registered as a study with the Core Outcome Measures in Effectiveness Trials Initiative. Publication of this study will increase the potential for comparative research to further understanding and prevent the empty pelvis syndrome.Trial registration number NCT05683795.

Background: Portal vein occlusion shortly before extended hepatic resections has hepatoprotective properties, but its molecular effects have not been elucidated. We characterized the impact of regenerative preconditioning by portal vein embolization (PVE) on hepatic energy metabolism and cytokine expression., Materials and Methods: About 90% hepatectomies were performed in normal pigs (Control) and in pigs that underwent a PVE 24 h before the surgery (n = 10/group). Blood biochemistry and coagulation, liver damage, liver function (ICG), hepatic content of adenine nucleotides, and hepatic expression of inflammatory mediators (RT-PCR and WB) were determined before the hepatectomy, 15 min, and 24 h later., Results: All PVE and hepatectomies were successfully accomplished. The 90% hepatectomy resulted in: Immediate reduction of ATP, leading to persistent decreases of energy load and ATP/ADP ratio up to the 24-h time-point; and pro-inflammatory expression profile of cytokines in the remnant liver. Prior performance of PVE attenuated the bioenergetic alterations and prevented many of the changes in hepatic cytokine expression., Conclusions: Regenerative preconditioning by PVE improved hepatic energy metabolism and modulated inflammatory mediators in the remnant liver in pigs undergoing major hepatectomies, potentially contributing to its hepatoprotective effects., (Copyright: © 2022 Permanyer.)

Background: The "Small-for-Size" syndrome is defined as a liver failure after a liver transplant with a reduced graft or after a major hepatectomy. The later coined "Small-for-Flow" syndrome describes the same situation in liver resections but based on hemodynamic intraoperative parameters (portal pressure > 20 mmHg and/or portal flow > 250 ml/min/100 g). This focuses on the damage caused by the portal hyperafflux related to the volume of the remnant., Methods: Relevant studies were reviewed using Medline, PubMed, and Springer databases., Results: Portal hypertension after partial hepatectomies also leads to a higher morbidity and mortality. There are plenty of experimental studies focusing on flow rather than size. Some of them also perform different techniques to modulate the portal inflow. The deleterious effect of high posthepatectomy portal venous pressure is known, and that is why the idea of portal flow modulation during major hepatectomies in humans is increasing in everyday clinical practice., Conclusions: Considering the extensive knowledge obtained with the experimental models and good results in clinical studies that analyze the "Small-for-Flow" syndrome, we believe that measuring portal flow and portal pressure during major liver resections should be performed routinely in extended liver resections. Applying these techniques, the knowledge of hepatic hemodynamics would be improved in order to advance against posthepatectomy liver failure.

Introduction: The term "Small-for-Flow" reflects the pathogenetic relevance of hepatic hemodynamics for the "Small-For-Size" syndrome and posthepatectomy liver failure. We aimed to characterize a large-animal model for studying the "Small-for-Flow" syndrome., Methods: We performed subtotal (90%) hepatectomies in 10 female MiniPigs using a simplified transection technique with a tourniquet. Blood tests, hepatic and systemic hemodynamics, and hepatic function and histology were assessed before (Bas), 15 min (t-15 min) and 24 h (t-24 h) after the operation. Some pigs underwent computed tomography (CT) scans for hepatic volumetry (n = 4) and intracranial pressure (ICP) monitoring (n = 3). Postoperative care was performed in an intensive care unit environment., Results: All hepatectomies were successfully performed, and hepatic volumetry confirmed liver remnant volumes of 9.2% [6.2-11.2]. The hepatectomy resulted in characteristic hepatic hemodynamic alterations, including portal hyperperfusion, relative decrease of hepatic arterial blood flow, and increased portal pressure (PP) and portal-systemic pressure gradient. The model reproduced major diagnostic features including the development of cholestasis, coagulopathy, encephalopathy with increased ICP, ascites, and renal failure, hyperdynamic circulation, and hyperlactatemia. Two animals (20%) died before t-24 h. Histological liver damage was observed at t-15 min and at t-24 h. The degree of histological damage at t-24 h correlated with intraoperative PP (r = 0.689, p = 0.028), hepatic arterial blood flow (r = 0.655, p = 0.040), and hepatic arterial pulsatility index (r = 0.724, p = 0.066). All animals with intraoperative PP > 20 mmHg presented liver damage at t-24 h., Conclusion: The present 90% hepatectomy porcine experimental model is a feasible and reproducible model for investigating the "Small-for-Flow" syndrome.

Background Context: Sacral chordoma is a rare entity with high local recurrence rates when complete resection is not achieved. To date, there are no series available in literature combining surgery and intraoperative radiotherapy (IORT)., Purpose: The objective of this study was to report the experience of our center in the management of sacral chordoma combining radical resection with both external radiotherapy and IORT., Study Design: This is a retrospective case series., Patient Sample: The patient sample included 15 patients with sacral chordoma resected in our center from 1998 to 2015., Outcome Measures: The outcome measures were overall survival (OS), disease-free survival (DFS), and rates of local and distant recurrences., Methods: We retrospectively reviewed the records of all the patients with sacral chordoma resected in our center from 1998 to December 2015. Overall survival, DFS, and rates of local and distant recurrences were calculated. Results between patients treated with or without IORT were compared., Results: A total of 15 patients were identified: 8 men and 7 women. The median age was 59 years (range 28-77). Intraoperative radiotherapy was applied in nine patients and six were treated with surgical resection without IORT. In 13 patients, we performed the treatment of the primary tumor, and in two patients, we performed the treatment of recurrence disease. A posterior approach was used in four patients. Wide surgical margins (zero residue) were achieved in six patients, marginal margins (microscopic residue) were achieved in seven patients, and there were no patients with intralesional (R2) margins. At a median follow-up of 38 months (range 11-209 months), the 5-year OS in the IORT group was 100% versus 53% in the group of non-IORT (p=.05). The median DFS in the IORT group was 85 months, and that in the non-IORT group was 41 months. In the group without IORT, two patients died and nobody died during the follow-up in the group treated with IORT. High-sacrectomy treated patients had a median survival of 41 months, and low-sacrectomy treated patients had a median survival of 90 months. Disease-free survival in patients without gluteal involvement was 100% at 5 years, and that in patients with gluteal involvement was 40%. All patients with a recurrence in our study had gluteal involvement., Conclusions: Multidisciplinary management of sacral chordoma seems to improve local control. The use of IORT, in our experience, is associated with an increase in OS and DFS. The level of resection and gluteal involvement seems to affect survival. The posterior approach is useful in selected cases. Multicenter studies should be performed to confirm the utility of IORT., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Portal vein embolization is performed weeks before extended hepatic resections to increase the future liver remnant and prevent posthepatectomy liver failure. Portal vein embolization performed closer to the operation also could be protective, but worsening of portal hyper-perfusion is a major concern. We determined the hepatic hemodynamic effects of a portal vein embolization performed 24 hours prior to hepatic operation., Methods: An extended (90%) hepatectomy was performed in swine undergoing (portal vein embolization) or not undergoing (control) a portal vein embolization 24 hours earlier (n = 10/group). Blood tests, hepatic and systemic hemodynamics, hepatic function (plasma disappearance rate of indocyanine green), liver histology, and volumetry (computed tomographic scanning) were assessed before and after the hepatectomy. Hepatocyte proliferating cell nuclear antigen expression and hepatic gene expression also were evaluated., Results: Swine in the control and portal vein embolization groups maintained stable systemic hemodynamics and developed similar increases of portal blood flow (302 ± 72% vs 486 ± 92%, P = .13). Portal pressure drastically increased in Controls (from 9.4 ± 1.3 mm Hg to 20.9 ± 1.4 mm Hg, P < .001), while being markedly attenuated in the portal vein embolization group (from 11.4 ± 1.5 mm Hg to 16.1 ± 1.3 mm Hg, P = .061). The procedure also improved the preservation of the hepatic artery blood flow, liver function, and periportal edema. These effects occurred in the absence of hepatocyte proliferation or hepatic growth and were associated with the induction of the vasoprotective gene Klf2., Conclusion: Portal vein embolization preconditioning represents a potential hepato-protective strategy for extended hepatic resections. Further preclinical studies should assess its medium-term effects, including survival. Our study also supports the relevance of hepatic hemodynamics as the main pathogenetic factor of post-hepatectomy liver failure., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to analyze long-term outcomes and prognostic factors associated with survival in patients with locoregional oligo-recurrent (LROR) pelvic malignancies treated in a multimodal protocol., Methods: Patients with an histologic diagnosis of LROR pelvic cancer (rectal 50 %, gynecological 50 %) with absence of distant metastases, undergoing surgery with radical intent and intraoperative radiotherapy (median dose 12.5 Gy) were considered eligible for participation in this study. Additionally, 48 % received external beam radiotherapy (EBRT) (median dose 50 Gy)., Results: From 1995 to 2012, a total of 143 patients from a single institution were analyzed. With a median follow-up time of 48 months (range 2-189), 5-year locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) were 53, 44, and 46 %, respectively. On multivariate analysis, no EBRT treatment to the locoregional (p ≤ 0.001), R1 margin status (p = 0.03), time interval from primary tumor diagnosis to LROR <24 months (p = 0.05), and fragmentation in the resected specimen (p = 0.004) retained significance in relation to LRC. On multivariate analysis we found that only R1 margin status (p = 0.003), primary tumor diagnosis to LROR <24 months (p = 0.02), and high histological grade (p = 0.02) were significantly associated with OS., Conclusions: From this analysis emerges the fact that EBRT influences local control but, given the high risk of distant metastases, DFS remains modest. Margin status, tumor fragmentation, no EBRT to the LR, and time interval from primary tumor diagnosis to LROR are the dominant factors for subsequent locoregional recurrence (LRR). Accordingly, future prospective studies might be designed which adapt treatment according to the predicted risk of subsequent LRR.

Purpose: To analyze long-term outcomes and prognostic factors in patients with paraaortic lymph-node oligometastases (LNO) from gynecological malignancies treated in a multimodal protocol., Methods: Patients with a histological diagnosis of LNO gynecological cancer [uterine cervix (n = 14, 40 %), endometrial (n = 18, 51 %), ovarian (n = 3, 9 %)] who underwent surgery with radical intent and intraoperative radiotherapy (IORT), median dose 12.5 Gy) were considered eligible for participation in this study. Additionally, 51 % received external-beam radiotherapy (EBRT)., Results: From 1997 to 2012, a total of 35 patients from a single institution were analyzed. With a median follow-up time of 55 months (range 2-148), 5-year loco-regional control (LRC), disease-free survival (DFS) and overall survival (OS) were 79, 44 and 49 %, respectively. On multivariate analysis, no EBRT treatment to the LNO (p = 0.03), and time interval from primary tumor diagnosis to LNO <24 months (p = 0.04) remained significantly associated with locoregional recurrence (LRR). We found on multivariate analysis that only R1 margin status (p = 0.01) was significantly associated with OS., Conclusion: From the current series of patients with gynecological LNO, it emerges the fact that EBRT promotes local control. Future prospective studies might be designed according to the predicted risk of LRR focusing on different subgroups.

Background: To analyze prognostic factors associated with long-term outcomes in patients with resected pancreatic cancer treated with chemotherapy (CT) and surgery with or without external beam radiotherapy (EBRT)., Patients and Methods: From January 1995 to December 2012, 95 patients with adenocarcinoma of the pancreas and locoregional disease [clinical stage IB-IIA (n = 45; 47%), IIB-IIIC (n = 50; 53%)] were treated with curative resection [R0 (n = 52; 55%), R1 (n = 43, 45%)] and CT with (n = 60; 63%) or without (n = 35; 37%) EBRT (45-50.4 Gy). Additionally, 29 patients (48%) also received a pre-anastomosis IOERT boost (applicator diameter size, 7-10 cm; dose, 10-15 Gy; beam energy, 9-18 MeV)., Results: With a median follow-up of 17.2 months (range, 1-182), 2-year overall survival (OS), disease-free survival (DFS), and locoregional control were 28, 20, and 53%, respectively. Univariate analyses showed that IIB-IIIC stage (HR, 2.23; p = 0.04), R1 margin resection status (HR, 2.09; p = 0.04), no vascular resection (HR, 0.42; p = 0.02), and not receiving external beam radiotherapy (HR, 2.70; p = 0.004) were associated with locoregional recurrence. In the multivariate analysis, only R1 margin resection status (HR, 2.63; p = 0.009) and not receiving EBRT (HR, 2.91; p = 0.002) retained significance with regard to locoregional recurrence. We observed no difference in toxicity between patients treated with or without EBRT (p = 0.44). Overall treatment mortality was 3%. No long-term treatment-related death occurred., Conclusions: Although adjuvant CT is still the standard of care for resected pancreatic tumors, OS remains modest owing to the high risk of distant metastases. Locoregional treatment needs to be tested in the context of more efficient systemic therapy.

Purpose: To analyze prognostic factors and long-term outcomes in patients with locally recurrent pelvic cancer (LRPC) treated with a multidisciplinary approach., Methods and Materials: From January 1995 to December 2011, 81 patients [rectal (47 %); gynecologic (39 %); retroperitoneal sarcoma (14 %)] underwent extended surgery [multiorgan (58 %), bone (35 %), vascular (9 %), soft tissue (63 %)] and intraoperative electron beam radiation therapy (IOERT) to treat recurrent tumors in the pelvic region. Thirty-five patients (43 %) received external beam radiotherapy (EBRT). Survival was estimated using the Kaplan-Meier method, and risk factors were identified using univariate and multivariate analysis., Results: Median follow-up was 39 months (6-189 months); the 1- 3- and 5-year rates of locoregional control (LRC) were 83, 53, and 41 %, respectively. Univariate Cox proportional hazard analysis revealed worse LRC in patients who did not receive integrated EBRT as rescue treatment of pelvic recurrence (p = 0.003) or underwent non-radical resection (p = 0.01). In the multivariate analysis EBRT, non-radical resection, and tumor fragmentation retained significance (p = 0.002, p = 0.004, and p = 0.05, respectively)., Conclusions: Radical resection, absence of tumor fragmentation and addition of EBRT for rescue are associated with improved LRC in patients with LRPC. Our results suggest that this group can benefit from EBRT combined with extended surgical resection and IOERT.

Background: Patients with locally advanced rectal cancer (LARC) have a dismal prognosis. We investigated outcomes and risk factors for locoregional recurrence (LRR) in patients treated with preoperative chemoradiotherapy (CRT), surgery and IOERT., Methods: A total of 335 patients with LARC [⩾cT3 93% and/or cN+ 69%) were studied. In multivariate analyses, risk factors for LRR, IFLR and OFLR were assessed., Results: Median follow-up was 72.6 months (range, 4-205). In multivariate analysis distal margin distance ⩽10 mm [HR 2.46, p = 0.03], R1 resection [HR 5.06, p = 0.02], tumor regression grade 1-2 [HR 2.63, p = 0.05] and tumor grade 3 [HR 7.79, p < 0.001] were associated with an increased risk of LRR. A risk model was generated to determine a prognostic index for individual patients with LARC., Conclusions: Overall results after multimodality treatment of LARC are promising. Classification of risk factors for LRR has contributed to propose a prognostic index that could allow us to guide risk-adapted tailored treatment., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The size of the remnant liver after an extended hepatectomy is currently the main limiting factor for performing curative hepatic surgery in patients with tumors and liver metastasis. The current guidelines for extended hepatectomies require that the future remnant liver volume needs to be higher than 20% of the original liver in healthy organs, of 30% in livers with steatosis or exposed to chemotherapy, and of 40% in patients with cirrhosis in order to prevent the "small-for-size" syndrome, characterized by the development of liver dysfunction with ascites, coagulopathy and cholestasis. Observations from the use of small liver grafts in liver transplantation and an increased surgical experience has improved our understanding of the mechanisms responsible for the development of liver dysfunction after extended hepatectomies. Increasing the size of the future liver remnant, the introduction of the "small-for-flow" concept with the perioperative monitoring and modulation of portal blood flow and pressure, and the exploration of the potential effects of regeneration preconditioning, are all promising strategies that could expand the indications and increase the safety of liver surgery., (© 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background and Purpose: It has been previously reported that a short FOLFOX-4 induction significantly improves pathologic complete response in locally advanced rectal cancer (LARC) patients treated with preoperative chemoradiation (CRT). In a larger and updated patient series, we analyzed FOLFOX-4 efficacy in terms of sphincter preservation and long-term outcomes., Patients and Methods: From January 1995 to December 2010, 335 LARC patients were treated with preoperative chemoradiation (4500-5040 cGy). Starting in May 2001, 207 consecutive patients additionally received induction FOLFOX-4. Surgery was performed 6 weeks (range 3-12 weeks) after chemoradiation., Results: Incidence of total tumor (63 vs. 54 %, p = 0.02) and nodal downstaging (60 vs. 43 %, p = 0.002) was significantly increased by induction FOLFOX-4. In an analysis of tumors located below 5 cm from the anal verge (n = 114, 34 %), sphincter preservation was feasible in 30 % in the FOLFOX-4 versus 13 % in the upfront CRT group (p = 0.04). Median follow-up time for the entire cohort of patients was 72.6 months (range 4-205 months). FOLFOX-4 was not associated with superior locoregional control (HR 0.88, p = 0.78), disease-free survival (HR 0.83, p = 0.55), distant metastases-free survival (HR 0.94, p = 0.81), or cancer-specific survival (HR 0.70, p = 0.15)., Conclusion: Short-intense induction FOLFOX-4 significantly improves downstaging and sphincter preservation in low rectal tumors. Long-term outcomes were not improved in the FOLFOX-4 group of patients.

Purpose: The goal of the present study was to analyze prognostic factors in patients treated with external-beam radiation therapy (EBRT), surgical resection and intraoperative electron-beam radiotherapy (IOERT) for oligorecurrent gynecological cancer (ORGC)., Patients and Methods: From January 1995 to December 2012, 61 patients with ORGC [uterine cervix (52 %), endometrial (30 %), ovarian (15 %), vagina (3 %)] underwent IOERT (12.5 Gy, range 10-15 Gy), and surgical resection to the pelvic (57 %) and paraaortic (43 %) recurrence tumor bed. In addition, 29 patients (48 %) also received EBRT (range 30.6-50.4 Gy). Survival outcomes were estimated using the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses., Results: Median follow-up time for the entire cohort of patients was 42 months (range 2-169 months). The 10-year rates for overall survival (OS) and locoregional control (LRC) were 17 and 65 %, respectively. On multivariate analysis, no tumor fragmentation (HR 0.22; p = 0.03), time interval from primary tumor diagnosis to locoregional recurrence (LRR) < 24 months (HR 4.02; p = 0.02) and no EBRT at the time of pelvic recurrence (HR 3.95; p = 0.02) retained significance with regard to LRR. Time interval from primary tumor to LRR < 24 months (HR 2.32; p = 0.02) and no EBRT at the time of pelvic recurrence (HR 3.77; p = 0.04) showed a significant association with OS after adjustment for other covariates., Conclusion: External-beam radiation therapy at the time of pelvic recurrence, time interval for relapse ≥ 24 months and not multi-involved fragmented resection specimens are associated with improved LRC in patients with ORGC. As suggested from the present analysis a significant group of ORGC patients could potentially benefit from multimodality rescue treatment.

Background: In selected patients with rectal cancer, laparoscopic surgery is as safe as open surgery, with similar resection margins and completeness of resection. In addition, recovery is faster after laparoscopic surgery. We analyzed long-term outcomes in a group of patients with locally advanced rectal cancer (LARC) treated with preoperative therapy followed by laparoscopic surgery and intraoperative electron-beam radiotherapy (IOERT)., Methods and Materials: From June 2005 to December 2010, 125 LARC patients were treated with 2 induction courses of FOLFOX-4 (oxaliplatin 85 mg/m(2)/d1, intravenous leucovorin at 200 mg/m(2)/d1-2, and an intravenous bolus of 5-fluorouracil 400 mg/m(2)/d1-2) and preoperative chemoradiation (4,500-5,040 cGy) followed by total mesorectal excision (laparoscopic, 35 %; open surgery, 65 %) and a presacral boost with IOERT., Results: Patients in the laparoscopic surgery group lost less blood (median 200 vs 350 mL, p < 0.01) and had a shorter hospital stay (7 vs 11 days; p = 0.02) than those in the open surgery group. Laparoscopic procedures were shorter than open surgery procedures (270 vs 302 min; p = 0.67). Postoperative morbidity (32 vs 44 %; p = 0.65), RTOG grade ≥3 acute toxicity (25 vs 25 %; p = 0.97), and RTOG grade ≥3 chronic toxicity (7 vs 9 %; p = 0.48) were similar in the laparoscopy and open surgery groups. The median follow-up time for the entire cohort of patients was 59.5 months (range 7.8-90); no significant differences were observed between the groups in locoregional control (HR 0.91, p = 0.89), disease-free survival (HR 0.80, p = 0.65), and overall survival (HR 0.67, p = 0.52)., Conclusions: Postchemoradiation laparoscopically assisted IOERT is feasible, with an acceptable risk of postoperative complications, shorter hospital stay, and similar long-term outcomes when compared to the open surgery approach.

Background/objectives: To analyze prognostic factors associated with long-term outcomes in patients with pancreatic cancer treated with chemoradiation therapy (CRT) and surgery with or without intraoperative electron beam radiotherapy (IOERT)., Patients and Methods: From January 1995 to December 2012, 60 patients with adenocarcinoma of the pancreas and locoregional disease (clinical stage IB [n = 13; 22%], IIA [n = 16; 27%], IIB [n = 22; 36%], IIIC [n = 9; 15%]) were treated with CRT (45-50.4 Gy before surgery [n = 19; 32%] and after surgery [n = 41; 68%]) and curative resection (R0 [n = 34; 57%], R1 [n = 26, 43%]). Twenty-nine patients (48%) also received a pre-anastomosis IOERT boost (applicator diameter size, 7-10 cm; dose, 10-15 Gy; beam energy, 9-18 MeV)., Results: With a median follow-up of 15.9 months (range, 1-182), 5-year overall survival (OS), disease-free survival (DFS), and locoregional control were 20%, 13%, and 58%, respectively. Univariate analyses showed that R1 margin resection status (HR, 3.17; p = 0.04), not receiving IOERT (HR, 7.33; p = 0.01), and postoperative CRT (HR, 5.12; p = 0.04) were associated with a higher risk of locoregional recurrence. In the multivariate analysis, only margin resection status (HR, 3.0; p = 0.05) and not receiving IOERT (HR, 6.75; p = 0.01) retained significance with regard to locoregional recurrence. Postoperative mortality and perioperative complications were 3% (n = 2) and 43% (n = 26)., Conclusions: Although local control is good in the radiation-boosted area, OS remains modest owing to high risk of distant metastases. Intensified locoregional treatment needs to be tested in the context of more efficient systemic therapy., (Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objective: To analyze prognostic factors in patients treated with intraoperative electrons containing resective surgical rescue of locally recurrent gynecological cancer (LRGC)., Methods: From January 1995 to December 2012, 35 patients with LRGC [uterine cervix (57%), endometrial (20%), ovarian (17%), vagina (6%)] underwent extended [multiorgan (54%), bone (9%), soft tissue (54%), vascular (14%)] surgery and intraoperative electron-beam radiation therapy [IOERT (10-15 Gy)] to the pelvic recurrence tumor bed. Sixteen (46%) patients also received external beam radiation therapy [EBRT (30.6-50.4 Gy)]. Survival outcomes were estimated using the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses., Results: Median follow-up time for the entire cohort of patients was 46 months (range, 3-169). Ten-year rates for locoregional control (LRC) and overall survival (OS) were 58 and 16%, respectively. On multivariate analysis non-EBRT at the time of pelvic re-recurrence [HR 4.15; p = 0.02], no tumor fragmentation [HR 0.13; p=0.05] and time interval from primary tumor to LRR < 24 months [HR 5.16; p=0.01], retained significance with regard to LRR. Non-EBRT at the time of pelvic re-recurrence [HR 4.18; p=0.02] and time interval from primary tumor to LRR < 24 months [HR 6.67; p=0.02] showed a significant association with OS after adjustment for other covariates., Conclusions: EBRT treatment integrated for rescue, time interval for relapse ≥ 24 months, and not multi-involved fragmented resection specimens are associated with improved LRC in patients with LRGC in the pelvis. Present results suggest that a significant group of patients may benefit from EBRT treatment integrated with extended surgery and IOERT., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To analyze prognostic factors associated with survival in patients after intraoperative electrons containing resective surgical rescue of locally recurrent rectal cancer (LRRC)., Methods and Materials: From January 1995 to December 2011, 60 patients with LRRC underwent extended surgery (n=38: multiorgan [43%], bone [28%], soft tissue [38%]) or nonextended (n=22) surgical resection, including a component of intraoperative electron-beam radiation therapy (IOERT) to the pelvic recurrence tumor bed. Twenty-eight (47%) of these patients also received external beam radiation therapy (EBRT) (range, 30.6-50.4 Gy). Survival outcomes were estimated by the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses., Results: The median follow-up time was 36 months (range, 2-189 months), and the 1-year, 3-year, and 5-year rates for locoregional control (LRC) and overall survival (OS) were 86%, 52%, and 44%; and 78%, 53%, 43%, respectively. On multivariate analysis, R1 resection, EBRT at the time of pelvic rerecurrence, no tumor fragmentation, and non-lymph node metastasis retained significance with regard to LRR. R1 resection and no tumor fragmentation showed a significant association with OS after adjustment for other covariates., Conclusions: EBRT treatment integrated for rescue, resection radicality, and not involved fragmented resection specimens are associated with improved LRC in patients with locally recurrent rectal cancer. Additionally, tumor fragmentation could be compensated by EBRT. Present results suggest that a significant group of patients with LRRC may benefit from EBRT treatment integrated with extended surgery and IOERT., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Introduction: To report feasibility, tolerance, anatomical sites of upper abdominal locoregional recurrence and long-term outcome of gastric cancer patients treated with surgery and a component of intraoperative electron beam radiotherapy (IORT)., Materials and Methods: From January 1995 to December 2010, 32 patients with primary gastric adenocarcinoma treated with curative resection (R0) [total gastrectomy (n = 9; 28 %), subtotal (n = 23; 72 %) and D2 lymphadenectomy in all patients] and apparent disease confined to locoregional area [Stage: II (n = 15; 47 %), III (n = 17; 53 %)] were treated with a component of IORT (IORT applicator size 5-9 cm in diameter, dose 10-15 Gy, beam energy 6-5 MeV) over the celiac axis and peripancreatic nodal areas. Sixteen (50 %) patients also received adjuvant treatment (external beam radiotherapy n = 6, chemoradiation n = 9, chemotherapy alone n = 1)., Results: With a median follow-up time of 40 months (range, 2-60), locoregional recurrence was observed in five (16 %) patients (4 nodal in hepatic hilum and 1 anastomotic). Only pN1 patients developed locoregional relapse. No recurrence was observed in the IORT-treated target volume (celiac trunk and peripancreatic nodes). Overall survival at 5 years was 54.6 % (95 % CI: 48.57-60.58). Postoperative mortality was 6 % (n = 2) and postoperative complications 19 % (n = 6)., Conclusions: It is feasible to integrate IORT as a component of radiotherapy in combined modality therapy of gastric cancer. Local control is high in the radiation boosted area, but marginal regional extension (in particular, involving the hepatic hilum) might be considered as part of the anatomic IORT target volume at risk in pN+ patients.

Background: To report feasibility, tolerance, anatomical topography of locoregional recurrence (LRR), and long-term outcome for esophageal and esophagogastric (EG) cancer patients treated with preoperative chemoradiation (CRT) and surgery with or without a radiation boost of intraoperative electron beam radiotherapy (IOERT)., Methods: From January 1995 to December 2010, 53 patients with primary esophageal (n = 26; 44 %) or EG carcinoma (n = 30; 56 %), and disease confined to locoregional area [clinical stage: IIb (n = 30; 57 %), IIIa (n = 14; 26 %), IIIb (n = 6; 11 %), IIIc (n = 3; 6 %)], were treated with preoperative CRT, curative (R0) resection with an extended (two-field) lymph node dissection in all cases. Thirty-seven patients also received a preanastomotic reconstruction IOERT boost (applicator diameter size 6-9 cm, dose 10-15 Gy, beam energy 6-15 MeV) over the tumor bed in the mediastinum and upper abdominal lymph node area., Results: With a median follow-up time of 27.9 months (range, 0.2-148), LRR rate was 15 % (n = 8). Five-year overall survival (OS) and disease-free survival was 48 and 36 %, respectively. Univariate log-rank analyses showed that receiving IOERT was associated with lower risk of LRR (p = 0.004). On multivariate analysis, only the IOERT group retained significance in relation to LRR (odds ratio, 0.08; 95 % confidence interval, 0.01-0.48; p = 0.01). Postoperative mortality and perioperative complications were 11 % (n = 6) and 30 % (n = 16)., Conclusions: Local control is high in the radiation-boosted area, but OS remains modest, given the high risk of distant metastases. Intensified locoregional treatment needs to be tested in the context of more efficient concurrent, neo-, and adjuvant systemic therapy.

The "small-for-size" syndrome and "post-hepatectomy liver failure" refers to the development of liver failure (hyperbilirubinemia, coagulopathy, encephalopathy and refractory ascites) resulting from the reduction of liver mass beyond a certain threshold. This complication is associated with a high mortality and is a major concern in liver transplantation involving reduced liver grafts from deceased and living donors as well as in hepatic surgeries involving extended resections of liver mass. The limiting threshold for liver resection or transplantation is currently predicted based on the mass of the remnant liver (or donor graft) in relation to the body weight of the patient, with a ratio above 0.8 being considered safe. This approach, however, has proved inaccurate, because some patients develop the "small-for-size" syndrome despite complying with the "safe" threshold while other patients who surpass the threshold do not develop it. We hypothesize that the development of the "small-for-size" syndrome is not exclusively determined by the ratio of the mass of the liver remnant (or graft) to the body weight, but it is instead strictly determined by the hemodynamic parameters of the hepatic circulation. This hypothesis is based in recent clinical and experimental reports showing that relative portal hyperperfusion is a critical factor in the development of the "small-for-size" syndrome and that maneuvers that manipulate the hepatic vascular inflow are able to prevent the development of the syndrome despite liver-to-body weight ratios well below the "limiting" threshold. Measurements of hepatic blood flow and pressure, however, are not routinely performed in hepatic surgeries. Focusing on the "flow" rather than in the "size" may improve our understanding of the pathophysiology of the "small-for-size" syndrome and "post-hepatectomy liver failure" and it would have important implications for the clinical management of patients at risk. First, hepatic hemodynamic parameters would have to be measured in hepatic surgeries. Second, these parameters (in addition to liver mass) would be the principal basis for deciding the "safe" threshold of viable liver parenchyma. Third, the hepatic hemodynamic parameters are amenable to manipulation and, consequently, the "safe" threshold may also be manipulated. Shifting the paradigm from "small-for-size" to "small-for-flow" syndrome would thus represent a major step for optimizing the use of donor livers, for expanding the indications of hepatic surgery, and for increasing the safety of these procedures., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the feasibility and long-term outcome of surgery combined with intraoperative electron radiotherapy (IOERT) as rescue treatment in patients with recurrent and/or metastatic oligotopic extrapelvic cancer., Methods and Materials: From April 1996 to April 2010, we treated 28 patients using 34 IOERT procedures. The main histopathology findings were adenocarcinoma (39%) and squamous cell carcinoma (29%). The original cancer sites were gynecologic (67%), urologic (14%) and colorectal (14%). The location of recurrence was the para-aortic region in 53.5% of patients., Results: Median follow-up was 39 months (1-84 months), during which time 14% of patients experienced local recurrence and 53.5% developed distant metastasis. Overall survival at 2 and 5 years was 57% and 35% respectively. At the time of the analysis, 13 patients were alive, 6 for more than 55 months of follow-up. Local control was not significantly affected by the following histopathologic characteristics of the resected surgical specimen: number of fragments submitted for pathology study (1 to >6), maximal tumor dimension (≤ 2 to ≥ 6 cm), rate of involved nodes (0-100%) and involved resection margin (local recurrence 23% vs 7%; p = 0.21). Local recurrence was significantly affected by microscopic cancer in more than 50% of specimen fragments (38% vs 9%, p = 0.02)., Conclusions: IOERT for recurrence of oligotopic extrapelvic cancer increased long-term survival in patients with controlled cancer and appears to compensate for some adverse prognostic features in local control. Individualized treatment strategies for this heterogeneous category of patients with recurrent cancer will make it possible to optimize results., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Peritoneal Malignant Disease (PMD) is the presence of tumoral tissue on the peritoneal surface from primary tumors or tumors from other locations (e.g. digestive or gynecologic). It is a regional disease with poor prognosis when treated with repeated "debulking" and traditional systemic chemotherapy. Cytoreduction plus hyperthermic intraperitoneal chemotherapy (HIPEC) is a combined multimodal regional procedure aimed at reducing the macroscopic tumoral mass as much as possible and treating with chemotherapy the microscopic disease that is out of the scope of the surgeon. This combined treatment may change the natural history of PMD, it is translated into a higher overall survival and cancer-free survival and it offers the option of cure in selected cases. The high-complexity procedure is also associated with complications and mortality, but in similar rates as other major oncologic procedures.

Retrorectal cystic hamartomas (tailgut cysts) are rare congenital lesions thought to arise from remnants of the embryonic postanal gut. They predominantly occur as asymptomatic retrorectal multicystic masses in women. The treatment of choice is by complete surgical excision. The most important complications of these cysts are infection with a secondary fistula and malignant degeneration. The differential diagnosis includes a wide variety of conditions that occur in the retrorectal space. In this article, 3 cases showing different surgical technical aspects of treatment are presented. In addition, the aetiopathogenic features and histopathological appearance, clinical presentation and complications, imaging features and differential diagnosis of tailgut cysts are described.

Introduction: Sarcomas are rare tumors that develop from mesenchymal cells. Their management is difficult due to their changing histology, location, and behavior. In this article, we discuss the use of two intraoperative therapeutic intensification techniques, intraoperative radiotherapy (IORT) and hyperthermic intraoperative intraperitoneal chemotherapy (HIIC), in the treatment of locally advanced abdominal sarcomas and peritoneal sarcomatosis., Material and Methods: We analyzed a series of 20 consecutive patients diagnosed with advanced abdominal sarcoma and 5 patients with a diagnosis of peritoneal sarcomatosis who were evaluated and treated in our department from December 1996 to October 2005. In advanced abdominal sarcoma, we performed complete or maximal resection followed by IORT. In peritoneal sarcomatosis we performed massive cytoreduction followed by HIIC., Results: The survival rate in advanced abdominal sarcomas without sarcomatosis was 65% at 26 months. Among the 5 patients diagnosed with peritoneal sarcomatosis, 3 were alive, and 2 were without recurrence at 20 months of follow-up., Conclusions: IORT associated with radical surgery seems to improve local control and survival in advanced abdominal sarcomas. Maximal cytoreduction plus HIIC used as treatment of peritoneal sarcomatosis is a feasible technique that offers a therapeutic option with curative intent.

Purpose: Fluoropyrimidine-radiosensitizing agents in conjunction with preoperative radiotherapy have proven to induce tumor and nodal downstaging effects, sphincter preservation promotion, and mid-term favorable survival rates. Intraoperative electron beam radiation therapy may improve pelvic control in patients with locally advanced rectal cancer stages. Potential predictive factors for response and disease-free survival, with intense local multidisciplinary approach, are analyzed., Methods and Materials: One hundred fifteen patients with rectal cancer were treated with oral 5-fluorouracil or Tegafur with preoperative radiotherapy, surgery, and intraoperative electron beam radiation therapy to identify potential pre- and on-treatment characteristics that might be of prognostic value for disease outcome. Univariate and multivariate analyses were performed., Results: Older patients and those treated with Tegafur were more likely to achieve a major histologic response, categorized as persistence of minimal residual microscopic disease foci in the surgical specimen ("mic" response). Factors unfavorably associated with disease-free survival in the multivariate model were male gender and persistence of macroscopic disease in the rectal wall ("mac" response). Accordingly, 3-year disease-free survival rates in the groups of patients with 0, 1, or 2 of these risk factors were 100%, 81%, and 53%, respectively (p < 0.001)., Conclusions: Females with an intense pathologic response (pT(mic) residue) to preoperative chemoradiotherapy have an excellent 3-year disease-free survival. This information might be of interest for stratification of patients in the development of adjuvant treatment trials.

As a contribution to International Physics Year (2005), we performed a historical study of Einstein's final years and the diseases that required surgical treatment. Because of the particular circumstances of the age, two of the most famous surgeons of the time, Rudolph Nissen and Frank Glenn, as well as the well-known radiologist, Gustav Bucky, came together with Albert Einstein over the abdominal aortic aneurysm that ended his life in April 1955. We discuss little known or hitherto unpublished data and anecdotes about the physicist's final surgical disease.

A 47-year-old man with recurring vertebral hydatidosis was scheduled for surgical removal of cysts by an anterior approach. Anesthetic management included multimodal monitoring and prophylaxis for the most common neurological, hemodynamic, and respiratory complications, as well as for appropriate control of pain during and after surgery. The spine is a rare location for hydatid cysts. Treatment is surgical, although imidazoles are useful for prevention and protection against recurrence. The prognosis is good.

The early institutional experience in the neoadjuvant treatment of potentially resectable pancreatic carcinoma using oral Tegafur as radioenhancing agent is analyzed. Fifteen patients (10 male and 5 female, mean age of 61 years) were treated over a 30-month period. Tegafur dose was 1,200 mg/d along the external radiotherapy period (45-55 consecutive days). Preoperative radiotherapy achieved a total dose of 45 to 50 Gy (1.8 Gy/d). Intraoperative electron boost (10-15 Gy) was delivered at the time of surgery. Hematologic tolerance showed a significant decrease of neutrophil and platelet counts from the outset to the end of the neoadjuvant period (p = 0.001 and p = 0.004, respectively). Five grade III vomiting episodes (33%) were also registered. In 9 patients (60%), surgical resection was performed after chemoradiation. Three complete pathologic responses (pT0 specimens) were identified; in seven cases, the resection achieved tumor-free surgical margins of the specimen. With a median follow-up of 21 months, median survival time was 17 months, with actuarial rates of 45% at 1 year and 24% at 3 years. Median survival for the resected patients was 23 months, and for the unresected patients median survival was 8 months (p = 0.02). The overall median survival in completely resected patients was 28 months, with a 71% survival rate at 1 and 3 years. It is concluded that the treatment scheme described is feasible and acceptably tolerated. The use of oral Tegafur seems to induce results similar to those of other therapeutic protocols using intravenous radioenhancing chemotherapy.

Solitary and early brain metastases from colon carcinoma are unusual. This possibility must be kept in mind, in patients with cerebral metastasis of unknown adenocarcinoma. These patients could benefit from colonoscopy and CEA studies with the aim of achieving more early diagnosis and surgical resection. The case of a 48-year-old woman with brain metastasis diagnosed 4 months before the primary tumor, a colon cancer, is reported.

During a 3-year period between 1990 and 1993, 100 patients received orthotopic liver transplantation at the "Gregorio Marañón" University General Hospital. The mean age of the patients was relatively high (46.9 +/- 10 years), with an important number of cirrhotic patients (91%). The rate of primary liver failure was relatively low (4.5% of transplantations) although 12 cases with more than 55 years were included in the present series. Eleven retransplantations were performed, 8 for early failure of the graft and 3 for chronic failure. Postoperative complications of the graft were vascular in 9 cases, biliary in 17 cases, and acute rejection (cellular) in 70 patients, although only 50 of these patients required treatment with steroid boluses. Infections were diagnosed in 60 cases with 80% of major infections, 6 of them caused by Aspergillus fumigatus that were lethal in all the cases. Postoperative survival was 82%, 72%, 69% and 69% at 1 month, 6 months, 1 year and 2 years respectively.

From 1984 to 1991, 44 cirrhotic patients with gastrointestinal bleeding by esophagogastric varices (EGV) underwent emergency or elective calibrated portacaval shunt (CPS) with a prothesis of small diameter (8 and 10 mm) due to the impossibility of bleeding control by other conservative methods. In this series this procedure was found to be an effective alternative with acceptable operative mortality (20.4%), and a high rate of hepatic portal flow maintenance (72.2%) although a high incidence of postoperative hepatic encephalopathy (38.6%) of easy control was observed. The global probability of survival at 12 and 24 months was 74 and 64%, respectively. Survival at one and 2 years was significantly higher in patients of Child score A than those of score B (94 and 88% versus 73 and 56%). Patients of Child score C all died by the end of the first month thus suggesting that CPS should be performed in patients with good liver function (Child scores A and B).

Recurrence of hepatocellular carcinoma is rarely treated by surgical resection and has not been reported in the main series of liver transplantation. In this paper we present the case of a patient transplanted for hepatocellular carcinoma on cirrhosis who developed a tumoral recurrence in the transplanted liver four months later. The new tumor was removed by hepatectomy and the patient is free of tumor 24 months after resection. Surgical resection should be considered a treatment of tumoral recurrence after liver transplantation as is done after hepatectomy.

An epidemic outbreak of Methicillin-resistant Staphylococcus Aureus (MRSA) infections affecting liver transplantation patients was detected in our hospital. In this study we describe the special characteristics of the infections and the results of prophylactic treatment with Vancomycin. Between april 1990 and december 1991, 47 patients with mean age of 54.4 +/- 10 years underwent liver transplantation. The patients were included in two chronological groups: 1) Group I: 20 patients not treated prophylactically with Vancomycin; 2) Group II: 27 consecutive patients treated with Vancomycin. Systematical cultures of body fluids for bacteria and fungi were done in every patient, and were repeated after 24 hours. The cultures were repeated again in case of sepsis. Group I patients had a significantly higher frequency of MRSA infections than group II patients. Furthermore, in patients with MRSA infection, independently of the group, duration of transplantation (p < 0.01), reoperations (p < 0.001) and prophylactic treatment with Vancomycin (p < 0.001) were significative factors. In conclusion, Vancomycin appears to be an elective prophylactic antibiotic in case of high risk of MRSA sepsis after liver transplantation.

We developed a two-clamp technique to avoid stenoses in portal anastomoses during liver transplantation. A portal anastomosis is created with a continuous polypropylene suture. A second vascular clamp is placed on the donor portal vein before release of the recipient vein clamp. After release of the proximal clamp, the vein is allowed to distend to its maximal diameter, and the suture is gently tied. This technique was used in both portal and arterial anastomoses in 43 consecutive liver transplant recipients. No cases of postoperative stenosis or thrombosis were observed.

The Tc-99m HIDA scan is a valuable study after liver transplantation, associated with other image techniques. We have used this technique as a reliable and objective diagnostic method for biliary fistula after removal of the T-tube in 5 liver transplantation patients with pain after T-tube removal. All five patients who developed fistula not only were diagnosed immediately but, furthermore, the surgical technique was indicated by the gammagraphic study. After this experience, we propose to remove the T-tube during the Tc-99 HIDA scan.

From 1984 to 1987, 187 patients with acute pancreatitis (AP) were studied. All patients were stratified according to Ranson's criteria upon admission and were followed up by performing a CT scan weekly. One hundred and thirty-eight patients had 3 or less Ranson's criteria (non-severe acute pancreatitis = NSAP) and 49 presented 4 or more (severe acute pancreatitis = SAP). Ninety-six percent of the patients with (p less than 0.0001). Of the 49 patients with SAP, 39 developed pancreatic or peripancreatic NSAP were reactive to skin tests on the third week, while 4% remained anergic necrosis and were operated. Twenty-two of these patients had positive cultures demonstrating the presence of bacteria in the tissue samples. One hundred percent of the infected patients remained anergic until surgery, while only 40% of those with negative cultures remained anergic (p less than 0.05). Mortality rate correlated well with skin test responses, being 31% in anergic patients while only 5% in reactive subjects. Sustained anergic state (AS), sequentially checked, is associated with a high incidence of pancreatic sepsis.