Sex Disparities in Outcomes Following Major Liver Surgery: New Powers of Estrogen?

AIM: To explore potential sex differences in outcomes and regenerative parameters post major hepatectomies. BACKGROUND: Although controversial, sex differences in liver regeneration have been reported for animals. Whether sex disparity exists in human liver regeneration is unknown. METHODS: Data from consecutive hepatectomy patients (55 females, 67 males) and from the international ALPPS (Associating-Liver-Partition-and-Portal-vein-ligation-for-Staged-hepatectomy, a two stage hepatectomy) registry (449 females, 729 males) were analyzed. Endpoints were severe morbidity (≥3b Clavien-Dindo grades), Model for End-stage Liver Disease (MELD) scores, and ALPPS interstage intervals. For validation and mechanistic insight, female-male ALPSS mouse models were established. t , χ 2 , or Mann-Whitney tests were used for comparisons. Univariate/multivariate analyses were performed with sensitivity inclusion. RESULTS: Following major hepatectomy (Hx), males had more severe complications ( P =0.03) and higher liver dysfunction (MELD) P =0.0001) than females. Multivariate analysis established male sex as a predictor of complications after ALPPS stage 1 (odds ratio=1.78; 95% confidence interval: 1.126-2.89; P =0.01), and of enhanced liver dysfunction after stage 2 (odds ratio=1.93; 95% confidence interval: 1.01-3.69; P =0.045). Female patients displayed shorter interstage intervals (<2 weeks, 64% females versus 56% males, P =0.01), however, not in postmenopausal subgroups. In mice, females regenerated faster than males after ALPPS stage 1, an effect that was lost upon estrogen antagonism. CONCLUSIONS: Poorer outcomes after major surgery in males and shorter ALPPS interstage intervals in females not necessarily suggest a superior regenerative capacity of female liver. The loss of interstage advantages in postmenopausal women and the mouse experiments point to estrogen as the driver behind these sex disparities. Estrogen's benefits call for an assessment in postmenopausal women, and perhaps men, undergoing major liver surgery.

Pure laparoscopic vs. hand-assisted liver surgery for segments 7 and 8: propensity score matching analysis.

BACKGROUND: Laparoscopic liver resection of tumors located in segments 7 and 8 are considered a complex resection. The aim of this study was to compare the intraoperative and early postoperative outcomes of patients operated by pure laparoscopic (PLS) vs hand-assisted laparoscopic surgery (HALS). METHODS: From January 2003 to January 2021, we included patients with minimally invasive surgery for lesions located in segments 7 and 8. To overcome selection bias, we performed 1:1 propensity score matching (PSM) between HALS and PLS cohorts, including 30 patients in each of the groups. Of the 60 patients who underwent PSM, we compared the first 30 patients with the following 30 patients. RESULTS: A total of 79 LLRs were performed, 46 by HALS and 33 by PLS. After PSM, in the PLS cohort, cirrhosis was more frequent (33.3% vs. 13.3%, p = 0.02). The surgical time, blood loss, Pringle maneuver, clamping time, and morbidity were similar between both groups, but with a lower hospital stay in the PLS group (3 days vs. 4 days, p < 0.01). In the first 30 patients who underwent LLR, the use of PLS was lower than the use of HALS, increasing due to the learning curve (16.7% in the first period vs. 83.3% in the second period; p < 0.01). The hospital stay was lower in the second period due to the more frequent use of PLS (3 vs. 4 days, p < 0.01). CONCLUSION: PLS presents similar intraoperative and early postoperative results with lower hospital stay for lesions located in segments 7 and 8 compared to HALS. In centers with experience in LLRs, PLS could be performed safely in these segments.

Acute renal disease in patients with ovarian peritoneal carcinomatosis treated with cytoreduction and HIPEC: the influence of surgery and the cytostatic agent used.

BACKGROUND: The main objective of this study was to evaluate the differences between cisplatin and paclitaxel in the development of postoperative renal toxicity, using as a reference the RIFLE (Risk, Injury, Insufficiency, Loss, and End-stage renal function) and AKIN (Acute Kidney Injury Network) criteria in patients with primary or recurrent ovarian cancer with peritoneal dissemination treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: One hundred fifty-two patients who were treated between December 2007 and June 2017 were analyzed. RESULTS: Patients who received previous platinum-based chemotherapy had higher baseline creatinine levels than those who had not (p = 0.05). A total of 11 (7.2%) and 4 (2.6%) patients developed an acute renal dysfunction (ARD) during the postoperative period of cytoreduction and HIPEC according to the RIFLE and AKI criteria respectively. RIFLE detects a higher rate of ARD due to different parameters such as GFR (7.2% versus 2.6%, p = 0.016). Performing ostomy (p = 0.007; OR: 39.320; 95% CI = 2.74-56.13) and using of cisplatin during HIPEC treatment (p = 0.017; OR = 13.619; 95% IC = 1.600-25.95) were factors independently related to a higher rate of ARD. CONCLUSION: ARD has a multifactorial origin. Cisplatin was associated with the development of a higher rate of ARD than paclitaxel. Diagnosis of ARD did not correlate with worse survival figures.

[Giant lipomas or retroperitoneal liposarcomas? Controversies in their diagnosis and treatment]. / ¿Lipoma gigante o liposarcoma retroperitoneal? Controversias en su diagnóstico y tratamiento.

BACKGROUND: Retroperitoneal lipomas are extremely rare tumors that must be differentiated from well-differentiated liposarcomas (WD-LPS). OBJECTIVES: To summarize the evidence about giant retroperitoneal lipomas or liposarcomas; and to elaborate recommendations for their management. DATA SOURCES: A systematic literature search from January 1985 to December 2019 and a review of our own cases was performed. RESULTS: Our series comprises four patients, two females and two males. The diagnosis was incidental in two cases. The medium size was 26 cm, being two cases located exclusively in the retroperitoneum, one in the inguinal region and one in the buttock via pelvic space. All cases were surgically removed being confirmed the initial diagnosis of retroperitoneal lipomas in two cases, as the rest two cases were classified as WD_LPS after MDM2/CDK4 genetic analysis. The review of the available literature plus our own cases revealed 30 cases, of which 58% were woman. Only two cases were asymptomatic. The main symptom was abdominal mass (53%) followed by abdominal pain (40,6%). The median size of the lesions was 24,9 cm with a median weight of 4.576,3 g. All cases were surgically removed, being necessary to remove contiguous organs in only four cases (12,5%). CONCLUSIONS: Retroperitoneal lipoma is a rare tumor which must be differentiated from WD-LPS. This is a very difficult task, being necessary to determinate MDM2 status (by FISH or MLPA), present in liposarcoma but not in lipomas, for its correct diagnosis. The treatment must be based on a complete surgical resection with negative margins.

Preoperative transarterial chemoembolization for laparoscopic liver resection in Child A cirrhotic patients with hepatocellular carcinoma.

PURPOSE: Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) offers better short-term results than open surgery with similar long-term results although it is technically difficult due to the risk of bleeding. METHODS: This study included patients with HCC in Child A cirrhosis who underwent TACE before LLR between 2009 and 2019. The primary endpoint was to analyze the intraoperative and early results of this technique. We also analyzed the long-term outcomes. Patients with and without clinically significant portal hypertension (CSPH) were compared. RESULTS: A total of 44 cirrhotic patients with HCC were included (24 CSPH and 20 non-CSPH). The Pringle maneuver was used in two cases (4.5%), mean blood losses was 100 ml (range 50-200), and three patients (6.8%) required a blood transfusion. The degree of necrosis achieved was greater than 90% in 27 patients (61.4%). At 1, 3, and 5 years, overall survival was 97.7%, 81.5%, and 63.4%, respectively, and disease-free survival was 85.2%, 52.5%, and 34.5%, respectively. There were no statistically significant differences between non-CSPH and CSPH groups regarding intraoperative, early, and long-term outcomes. CONCLUSION: In our experience, TACE could be beneficial to perform LLR in HCC Child-Pugh A patients with and without CSPH without serious complications and similar oncological outcomes.

A New Surgical Technique Variant of Partial ALPPS (Tourniquet Partial-ALPPS).

OBJECTIVE: We present a new variant of partial-ALPPS (p-ALPPS) "Tourniquet partial-ALPPS (Tp-ALPPS)", with the aim of reducing aggressiveness during stage 1. SUMMARY BACKGROUND DATA: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) results in liver regeneration in only 9 days. Due to its high initial morbidity and mortality, less aggressive variants were designed. METHODS: A new surgical variant of ALPPS was designed consisting in introducing a Kelly forceps from the base of the liver, crossing the liver parenchyma through an avascular area. A 3-mm Vicryl (V152; Ethicon, Somerville, New Jersey, USA) tape is passed, and the tourniquet is then knotted. Six patients operated on by this new Tp-ALPPS surgical technique were compared to 6 patients operated on by Tourniquet ALPPS (T-ALPPS). RESULTS: There were no differences in volume increase at 10 days. During stage 1, blood losses and transfusion rates tended to be lower in the Tp-ALPPS group, without statistical differences. Surgical time was shorter in the Tp-ALPPS group than in T-ALPPS (90 min versus 135 min) (p < 0.023). In stage 2, blood losses and transfusion were similar in both groups, but surgical time tended to be higher in the Tp-ALPPS group, which could be related to the surgical technique performed. There were no differences in morbidity and mortality. CONCLUSIONS: Tp-ALPPS achieved a similar increase in volume as T-ALPPS but with a shorter stage 1 surgical and similar morbidity and mortality.

Perforación de intestino delgado secundaria a retención de cápsula endoscópica / No disponible

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Perforation of the small bowel secondary to capsule endoscopy retention.

A 71-year-old female with liver cirrhosis underwent a capsule endoscopy (CE) due to middle gastrointestinal bleeding. A neoplastic stenotic lesion showing stigmata of a recent hemorrhage was observed in jejunum and the capsule was retained.

Case report of Tourniquet ALPPS and simultaneous sleeve gastrectomy: A valuable association to achieve an adequate future liver remnant in obese patients.

INTRODUCTION: Obesity represents a risk factor in case of major hepatectomy, because the future liver remnant (FLR) must be proportional with body weight. To avoid post-hepatectomy liver failure, and further increase the ratio between FLR and body weight, we performed a bariatric procedure in the first stage of the ALPPS technique. PATIENT CONCERNS: Fifty-four-year-old woman, with morbid obesity (BMI 58.5) and type II diabetes mellitus, was scheduled for a major hepatectomy due to multiple colorectal liver metastases DIAGNOSIS:: Six months before, the patient was diagnosed with colorectal cancer and synchronous liver metastases. She was initially treated with sigmoidectomy and chemotherapy. After partial response of the liver metastases, we considered a liver resection but the FLR was very low, especially in relation to her BMI. INTERVENTION: We planned a novel approach and, for the first time, we performed a sleeve gastrectomy during the first stage of Tourniquet ALPPS (T-ALPPS). After achieving an adequate FLR, we successfully completed the major hepatectomy during the second stage of T-ALPPS. OUTCOME: The association between sleeve gastrectomy and T-ALPPS produced an increase of FLR/body weight ratio up to 0.8 that allowed completing a right trisectionectomy in the second stage of ALPPS. The major hepatectomy was performed without severe complications, and several months after surgery the patient is still alive without any recurrence Conclusion: Despite obesity represents a risk factor involved in the carcinogenesis, the role of the bariatric surgery in the oncological setting is not well established. In this clinical case, we benefited from the weight loss produced by bariatric surgery combined with an effective hypertrophy technique and chemotherapy. These findings suggest that bariatric surgery could be useful for obese patients with liver malignancy and need for extended hepatectomy.

Intraperitoneal hyperthermic chemotherapy after cytoreduction in patients with peritoneal metastases from endometrial cancer. The next frontier?

BACKGROUND: Endometrial cancer is the most common malignancy of the female genital tract. For cancers detected at an advanced stage or intraperitoneal relapse, the prognosis is poor. Optimal cytoreductive surgery (CRS) is the most accepted treatment; however, patients with advanced intraperitoneal disease might benefit from hyperthermic intraoperative peritoneal chemotherapy (HIPEC). The aim of this study was to analyze recurrence-free survival (RFS) after CRS and HIPEC in a large series of patients with peritoneal metastases from endometrial cancer. METHODS: Patients with a diagnosis of endometrial cancer with primary or recurrent peritoneal dissemination were included. All patients underwent CRS plus HIPEC. Data were prospectively collected in the Spanish Group of Peritoneal Oncological Surgery (GECOP) database. RESULTS: Forty-three patients with endometrial cancer and peritoneal metastasis were included. Fifteen patients (35%) were diagnosed with G3 endometrioid carcinomas and 28 (65%) with other non-endometroid histologies. A completeness of cytoreduction score of CC-0 was achieved in 41 patients (95%). RFS at 5 years was 23%, being factors related to worse RFS: treatment with preoperative chemotherapy (p = 0.027), resection of more than three peritoneal areas (p = 0.010), cytoreduction of the upper abdominal space (p = 0.023), HIPEC treatment with paclitaxel (p = 0.013), and the presence of metastatic lymph nodes (p = 0.029). CONCLUSIONS: Better RFS rates after CRS and HIPEC were observed for patients with the following characteristics: cytoreductive surgery without preoperative chemotherapy, complete surgery performed with limited surgical maneuvers, treated with cisplatin, and no lymph node metastases. SYNOPSIS: Endometrial cancer has a poor prognosis when diagnosed at advance stage. Patients with intraperitoneal metastases from endometrial cancer may benefit from CRS plus HIPEC with improvement in the recurrence-free survival results.

Peritoneal Surface Disease Severity Score (PSDSS), AGO-score and TIAN model in patients with platinum-sensitive recurrent ovarian cancer treated by cytoreductive surgery plus HIPEC.

In patients with platinum sensitive recurrent ovarian cancer selected for a secondary cytoreduction, the use of prognostic scores allows predicting the possibilities of a new complete cytoreduction. The aim of this work is to evaluate the usefulness of PSDSSov, the AGO-score and the TIAN-model as prognostic tools in these patients. Sixty four patients with recurrent platinum sensitive ovarian cancer treated by cytoreduction and HIPEC were analyzed between January 2008 and December 2016. Since 2012, the data needed to calculate the PSDSS, AGO-score and TIAN model were collected prospectively. Fifty patients (78%) received systemic chemotherapy before cytoreduction and HIPEC. In 57 patients (89%) a CC-0 was achieved. Patients with PSDSSov I-II and TIAN model of "low risk" had a DFS at 1 and 5 years of 71% and 57%, respectively, without reaching the median of DFS. PSDSSov is a useful prognostic tool and can be used in decision making in patients with peritoneal carcinomatosis due to recurrent platinum-sensitive ovarian cancer. Its combination with the Tian model makes it possible to identify patients with an especially favorable prognosis.

Long-Term Outcome After Conventional Two-Stage Hepatectomy Versus Tourniquet-ALPPS in Colorectal Liver Metastases: A Propensity Score Matching Analysis.

BACKGROUND: To compare the overall survival (OS) and disease-free survival (DFS) of Tourniquet-ALPPS (T-ALPPS) and conventional two-stage hepatectomy (TSH) in patients with colorectal liver metastases (CRLM). METHODS: A retrospective study from a prospectively collected database was performed between October 2000 and July 2016. TSH was performed before September 2011, after which time T-ALPPS became the technique of choice. A propensity score matching (PSM) was performed based on a 1:1 ratio with consideration of the following variables: number and size of metastases, bilobar disease presence, and chemotherapy received. RESULTS: Thirty-four patients received T-ALPPS; 41 patients received TSH. After PSM, 21 patients remained in each group, with 100% resectability in the T-ALPPS group and 90.5% resectability in the TSH group. The median OS for TSH was 41 months; for T-ALPPS, the median OS was 36 months (P = 0.925). The median DFS was 16 months in the TSH group; the median DFS was 9 months in the T-ALPPS group (P = 0.930). The 1-, 3-, and 5-year OS for TSH was 81%, 66.7%, and 23.8% vs. 76.2%, 57.1%, and 22.9% for T-ALPPS, respectively. The 1-, 3-, and 5-year DFS for TSH was 66.7%, 9.5%, and 5% vs. 44.6%, 11.1%, and 11.1% for T-ALPPS, respectively. The volume increase with T-ALPPS was superior to that with TSH (68% vs. 39%; P = 0.018). There were no differences in morbidity and mortality after stages 1 and 2. CONCLUSIONS: T-ALPPS produces a similar outcome to TSH, indicating that it could be a safe and effective alternative for curative hepatectomy for all patients.

Open versus minimally invasive liver surgery for colorectal liver metastases (LapOpHuva): a prospective randomized controlled trial.

OBJECTIVE: To present surgical and oncological outcomes using a prospective and randomized trial (LapOpHuva, NCT02727179) comparing minimally invasive liver resection (LLR) versus open liver resection (OLR) in patients with colorectal liver metastases (CRLM). METHODS: Between February 2005 and March 2016, 204 selected patients with CRLM were randomized and 193 were included: LLR (n = 96) and OLR (n = 97). The primary endpoint was to compare postoperative morbidity. Other secondary endpoints were oncological outcomes, use of the Pringle maneuver, surgical time, blood losses, transfusions, hospital stay, mortality and OS, and disease-free survival (DFS) at 3, 5, and 7 years. RESULTS: LLR presented with lower global morbidity (11.5% vs. 23.7%, p = 0.025) but with similar severe complications. Long-term survival outcomes were similar in both groups. The cumulative 1-, 3-, 5-, 7-year OS for LLR and OLR were 92.5%, 71.5%, 49.3%, 35.6% versus 93.6%, 69.7%, 47.4%, 35.5%, respectively (log-rank = 0.047, p = 0.82). DFS for LLR and OLR was 72.7%, 33.5%, 22.7%, and 20.8% versus 61.6%, 27.2%, 23.9%, and 17.9%, respectively (log-rank = 1.427, p = 0.23). LLR involved more use of the Pringle maneuver (15.5% vs. 30.2%, p = 0.025) and a shorter hospital stay (4 vs. 6 days, p < 0.001). There were no differences regarding surgical time, blood losses, transfusion, and mortality. CONCLUSIONS: In selected patients with CRLM, LLR presents similar oncological outcomes with the advantages of the short-term results associated with LLR.

ALPPS for hepatocarcinoma under cirrhosis: a feasible alternative to portal vein embolization.

Hepatocellular carcinoma (HCC) is one of the most common and malignant tumors. Preoperative portal vein embolization (PVE) is currently the most accepted treatment before major hepatic resection for HCC in patients with liver fibrosis or cirrhosis and associated insufficient future liver remnant (FLR). In the last decade, associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) technique has been described to obtain an increase of volume regarding PVE and a decrease of drop out. The initial excessive morbidity and mortality of this technique have decreased drastically due to a better selection of patients, the learning curve and the use of less aggressive variations of the original technique in the first stage. For both techniques a complete preoperative assessment of the FLR is the most important issue and only patients with and adequate FLR should be resected. ALPPS could be a feasible technique in very selected patients with HCC and cirrhosis. As long as it is performed in an experienced center could be used as a first choice technique versus PVE or could be used as a rescue technique in case of PVE failure.

The assessment of the Newborn Hearing Screening Program in the Region of Murcia from 2004 to 2012.

OBJECTIVES: Newborn (NB) auditory deficit has a prevalence of 1-2% in the world. Since the 1990s different screening programs have been put into practice. The Newborn Hearing Screening Program has been in operation since 2002 in our hospital (HCUVA) in Murcia (Spain) and two years later it was introduced into the whole of the Autonomous Community of the Region of Murcia as part of universal healthcare. The objective of this study was to analyze and assess its results. METHOD: The newborn (NB) population is divided into two groups: not-at-risk NBs and at-risk NBs. In the first case we carry out acoustic otoemissions (AOEs) 48 h after birth and depending on the result the child is either discharged or, in negative cases, the infant undergoes a series of tests in a period of 30-45 days to confirm or rule out the existence of hearing anomalies. In the at-risk group we combine AOEs with brain trunk potentials (BERA) following the stages in a decision tree diagram similar to the ones for not-at-risk children in order to provide a clinical diagnosis in the first three months of life. RESULTS: The screening performance was assessed for the 156,122 children studied, of which 151,258 belonged to the group of not-at-risk children; and 4864 to the group at risk of hypoacusia. As a result of the screening only 410 (0.26%) were sent to consultation, 213 in the not-at-risk group (0.14%) and 197 (24.7%) in the at-risk group. A total of 7452 false positives were identified (4.7%), 6951 (4.5%) in the not-at-risk group; and 501 (10.3%) in the group with risk factors; and there were 53 false negatives (0.03%). Sensitivity in the screening program was 88.5%, with a specificity of 95%. CONCLUSIONS: The Region of Murcia has a Newborn Hearing Screening Program with tests that provide a high level of sensitivity and specificity in accordance with the findings of the literature. Our results endorse the program and the patients were treated in a way that met the objective of providing a correct diagnosis and the appropriate therapeutic action.