"Small-for-Flow" Syndrome: Concept Evolution.

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.

Role of intraoperative radiotherapy in the treatment of sacral chordoma.

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.

Intraoperative electron-beam radiation therapy with or without external-beam radiotherapy in the management of paraaortic lymph-node oligometastases from gynecological malignancies.

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.

Preoperative chemoradiation with or without induction oxaliplatin plus 5-fluorouracil in locally advanced rectal cancer. Long-term outcome analysis.

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.

External-beam radiation therapy after surgical resection and intraoperative electron-beam radiation therapy for oligorecurrent gynecological cancer. Long-term outcome.

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.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of advanced epithelial ovarian carcinoma: upfront therapy, at first recurrence, or later?

AIM: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) has been proposed as treatment for advanced epithelial ovarian carcinoma (EOC). No consensus exists on when to administer CRS+HIPEC during the natural history of the disease, namely, as upfront therapy, at first recurrence, or at second or subsequent recurrence. PATIENTS AND METHODS: We analyzed a series of patients with advanced EOC collected prospectively in an institution with a peritoneal malignant disease treatment program. Patients were treated with CRS+HIPEC upfront, at first recurrence, and at second or subsequent recurrence. RESULTS: We treated 42 patients: 15 upfront, 19 at first recurrence, and 8 at second or subsequent recurrence. Cytoreduction was complete (CC0) in 75% of cases; residual disease was <2.5 mm (CC1) in 25%. Severe morbidity (CTCAE v.3.0, grade 3-4) was 26%, and hospital mortality was 7%. After a median follow-up of 24 months, median overall survival was 77.8 months for patients treated upfront, 62.8 months for patients treated at first recurrence, and 35.7 months for patients treated at second or subsequent recurrence. Disease-free survival was 21.1 months, 18 months, and 5.7 months, respectively. Overall survival in the upfront and first recurrence groups was similar, and statistically significant differences with the second recurrence group were identified (p<0.03). CONCLUSIONS: Treatment of advanced EOC using CRS+HIPEC is promising in terms of overall survival and disease-free survival when administered as upfront and at first recurrence therapy. These results warrant further evaluation in a randomized trial.

Intraoperative electron beam radiotherapy and extended surgical resection for gynecological pelvic recurrent malignancies with and without external beam radiation therapy: long-term outcomes.

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.

"Small-for-flow" syndrome: shifting the "size" paradigm.

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.

Intraoperative radiotherapy for the treatment of resectable locally advanced gastric adenocarcinoma: topography of locoregional recurrences and long-term outcomes.

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.

Intraoperative EBRT and resection for renal cell carcinoma : twenty-year outcomes.

PURPOSE: We report the outcomes of a multimodality treatment approach combining maximal surgical resection and intraoperative electron radiotherapy (IOERT) with or without external beam radiation therapy (EBRT) in patients with locoregionally (LR) recurrent renal cell carcinoma (RCC) after radical nephrectomy or LR advanced primary RCC. PATIENTS AND METHODS: From 1983 to 2008, 25 patients with LR recurrent (n = 10) or LR advanced primary (n = 15) RCC were treated with this approach. Median patient age was 60 years (range, 16-79 years). Fifteen patients (60%) received perioperative EBRT (median dose, 44 Gy). Surgical resection was R0 (negative margins) in 6 patients (24%) and R1 (residual microscopic disease) in 19 patients (76%). The median dose of IOERT was 14 Gy (range, 9-15). Overall survival (OS) and relapse patterns were calculated using the Kaplan-Meier method. RESULTS: Median follow-up for surviving patients was 22.2 years (range, 3.6-26 years). OS and DFS at 5 and 10 years were 38% and 18% and 19% and 14%, respectively. LR control (tumor bed or regional lymph nodes) and distant metastases-free survival rates at 5 years were 80% and 22%, respectively. The death rate within 30 days of surgery and IOERT was 4% (n = 1). Six patients (24%) experienced acute or late toxicities of grade 3 or higher according to the National Cancer Institute Common Toxicity Criteria (NCI-CTCAE) v4. CONCLUSION: In patients with LR recurrent or LR advanced primary RCC, a multimodality approach consisting of maximal surgical resection and IOERT with or without adjuvant EBRT yielded encouraging local control results, justifying further evaluation.

Surgery and intraoperative electron radiotherapy in recurrent or metastatic oligotopic extrapelvic cancer: long-term outcome.

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.

[Anterior surgical approach to T12 and L1 in recurring vertebral hydatidosis: anesthetic management]. / Hidatidosis vertebral recidivada a nivel T-12 y L-1 con abordaje quirúrgico anterior: manejo anestésico.

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.

[Early cerebral metastasis of colonic adenocarcinoma]. / Metástasis cerebral precoz en adenocarcinoma de colon.

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.

[Resection of recurrent hepatocarcinoma on a transplanted liver]. / Resección de hepatocarcinoma recidivante sobre hígado trasplantado.

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.

Two-clamp method to avoid portal anastomotic stenosis in 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 anergic state as a predictor of pancreatic sepsis.

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.

Predicting mortality based on body composition analysis.

The role of the Nae/Ke ratio (the ratio of exchangeable sodium to exchangeable potassium) was examined as a nutritional marker in surgical patients in relation to anthropometrical and biochemical indexes by its ability to identify patients at risk for mortality after hospitalization. In 73 patients with sepsis and malnutrition (Training Group, Madrid) the following were determined: percentage of recent weight loss, triceps skin fold, midarm muscle circumference, serum albumin, serum transferrin, delayed hypersensitivity skin test response, total lymphocytes, and Nae/Ke ratio by multiple isotope dilution. The predictive power of Nae/Ke ratio was so strong (F = 105.1; p less than 0.00001) that it displaced anthropometric, biochemical, and immunologic variables from the linear equation derived from stepwise discriminant analysis using hospital mortality as the dependent variable. A theoretical curve of expected deaths was developed, based on an equation obtained by logistic regression analysis: Pr/death/ = 1/(1 + e[11.8-5.2 Nae/Ke]). Pre- and post-test probabilities on that curve allowed us to determine two cut-off values, Nae/Ke ratios of 1.5 and 2.5, which were markers for nonrisk and mortality, respectively. The model was tested in a heterogeneous data base of surgical patients (n = 417) in another hospital (Validation Group, Montreal). For patients exhibiting an abnormal Nae/Ke ratio (greater than 1.2) and a greater than 10% of probability of death, 54 deaths were expected and 53 observed (X2 = 1.8 NS). Two tests confirmed the basic agreement between the model and its performance, a G statistic of -0.704 and the area beneath the "receiver-operating-characteristic" (ROC) curve (Az = 0.904 + 0.0516 for the Madrid group vs. Az = 0.915 + 0.0349 for the Montreal group, NS). It was concluded from this analysis that, compared with the usual anthropometric measurements, the Nae/Ke ratio, if available, is the best method for identifying malnourished patients at risk of dying.