Search

To date, no reports have indicated laparoscopic lymph node biopsies using Indocyanine green (ICG) in cases of lymphoproliferative disease. Preliminary data of patients undergoing fluorescence-guided laparoscopic lymph node biopsy (FGLLB) using ICG was retrospectively analysed from the multicentre registry FLABILY study. Between June 2022 and February 2024, 50 patients underwent FGLLB. The surgical biopsy aimed to re-stage lymphoproliferative disease for 25 patients and to establish a diagnosis in 25 patients. The median duration of the procedure was 65 ± 26.5 min. All the procedures were performed laparoscopically. One surgical conversion occurred due to bleeding. Median length of hospitalization was 1 ± 1.7 days. Two unrelated complications occurred in the immediate postoperative course. ICG was administrated preoperatively by means of an inguinal, perilesional, or intravenous injection according to the anatomical sites of the biopsy. Fluorescence was obtained in 43/50 (86%) of patients. A significant difference was highlighted in the appearance of fluorescence in sub-mesocolic lymph nodes compared to supra-mesocolic and mesenteric lymph nodes (41/49 (83.6%) vs. 13/22 (59%), p = 0,012). In 98% of cases, FGLLB provided the information necessary for the correct diagnosis. Fluorescence with ICG offers a simple and safe method for detecting pathological lymph nodes. FGLLB in suspected intra-abdominal lymphoma can largely benefit from this new opportunity which, to date, has not yet been tested. Further studies with a larger case series are needed to confirm its efficacy., (© 2024. The Author(s).)

Background: Cytoreductive surgery (CRS) combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a complex procedure that involves extensive peritoneal and visceral resections followed by intraperitoneal chemotherapy. The Enhanced Recovery After Surgery (ERAS) program aims to achieve faster recovery by maintaining pre-operative organ function and reducing the stress response following surgery. A recent publication introduced dedicated ERAS guidelines for CRS and HIPEC with the aim of extending the benefits to patients with peritoneal surface malignancies., Methods: A survey was conducted among 21 Italian centers specializing in peritoneal surface malignancies (PSM) treatment to assess adherence to ERAS guidelines. The survey covered pre/intraoperative and postoperative ERAS items and explored attitudes towards ERAS implementation., Results: All centers completed the survey, demonstrating expertise in PSM treatment. However, less than 30 % of centers adopted ERAS protocols despite being aware of dedicated guidelines. Preoperative optimization was common, with variations in bowel preparation methods and fasting periods. Intraoperative normothermia control was consistent, but fluid management practices varied. Postoperative practices, including routine abdominal drain placement and NGT management, varied greatly among centers. The majority of respondents expressed an intention to implement ERAS, citing concerns about feasibility and organizational challenges., Conclusions: The study concludes that Italian centers specialized in PSM treatment have limited adoption of ERAS protocols for CRS ± HIPEC, despite being aware of guidelines. The variability in practice highlights the need for standardized approaches and further evaluation of ERAS applicability in this complex surgical setting to optimize patient care., Competing Interests: Declaration of competing interest The authors have no conflicts of interest or financial ties to disclose., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Isolated limb perfusion (ILP) is a well-established surgical procedure for the administration of high dose chemotherapy to a limb for the treatment of advanced extremity malignancy. Although the technique of ILP was first described over 60 years ago, ILP is utilised in relatively few specialist centres, co-located with tertiary or quaternary cancer centres. The combination of high dose cytotoxic chemotherapy and the cytokine tumour necrosis factor alpha (TNFα), mandates leakage monitoring to prevent potentially serious systemic toxicity. Since the procedure is performed at relatively few specialist centres, an ILP working group was formed with the aim of producing technical consensus guidelines for the procedure to streamline practice and to provide guidance for new centres commencing the technique., Methods: Between October 2021 and October 2023 a series of face to face online and hybrid meetings were held in which a modified Delphi process was used to develop a unified consensus document. After each meeting the document was modified and recirculated and then rediscussed at subsequent meeting until a greater than 90% consensus was achieved in all recommendations., Results: The completed consensus document comprised 23 topics in which greater than 90% consensus was achieved, with 83% of recommendations having 100% consensus across all members of the working group. The consensus recommendations covered all areas of the surgical procedure including pre-operative assessment, drug dosing and administration, perfusion parameters, hyperthermia, leakage monitoring and theatre logistics, practical surgical strategies and also post-operative care, response evaluation and staff training., Conclusion: We present the first joint expert-based consensus statement with respect to the technical aspects of ILP that can serve as a reference point for both existing and new centres in providing ILP., Competing Interests: Declaration of competing interest Angela Märten works as a consultant for Belpharma SA., (© 2024 Published by Elsevier Ltd.)

Locally advanced breast cancer (LABC) is a complex disease that requires a multidisciplinary approach. Neoadjuvant chemotherapy (NAC) is usually performed in order to achieve loco-regional radical resection; although its importance in the multidisciplinary approach to LABC is well recognized, a small number of patients show Progressive Disease (PD). No standard salvage treatment (ST) has been defined and different strategies can be adopted, such as second-line systemic therapies, radiation therapy, and surgery. Herein, a case of LABC in PD during NAC is reported with a literature review, with the aim of highlighting the importance of a tailored multidisciplinary treatment for each patient.

Background: Due to delayed diagnosis and a lower surgical indication rate, left-sided pancreatic ductal adenocarcinoma (PDAC) is often associated with a poor prognosis in comparison to pancreatic head tumors. Multi-visceral resections (MVR) associated with distal pancreatectomy could be proposed for patients presenting with locally infiltrating disease., Methods: We retrospectively analyzed a multi-centric cohort of left-sided PDAC patients operated on from 2009 to 2020. Thirteen European high-volume HPB centers participated in this study. We analyzed patients who underwent distal pancreatectomy (DP) associated with MVR and compared them to standard DP patients., Results: Among 258 patients treated curatively for PDAC of the body and tail, 28 patients successfully underwent MVR. A longer operative time was observed in the MVR group (295 min +/- 74 vs. 250 min +/- 96, p= 0.248). The post-operative complication rate was comparable between the two groups (46.4% in the MVR group vs. 62.2% in the control group, p= 0.108). The incidence of positive margin (R1) was similar between the two groups (28.6% vs. 26.6%; p=0.827). After a median follow-up of 25 (9-111) months, overall survival was comparable between the two groups (p= 0.519)., Conclusions: Multi-visceral resection in left-sided pancreatic ductal adenocarcinoma is safe and feasible and should be considered in selected cases as it seems to provide acceptable surgical and oncological outcomes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Indocyanine Green (ICG) fluorescence-guided surgery is widely used for intraoperative visualization of lymphatic structures. To date, there are no reports indicating this dye being used in lymph node biopsies for suspected or relapsed lymphoma., Methods: Between October 2021 and June 2022, 12 patients underwent a fluorescence-guided laparoscopic lymph node biopsy (FGLLB) using ICG. The following was retrospectively evaluated: the dosage of ICG, the injection site, the number of patients where fluorescence was obtained after ICG administration, and additionally, the parameters indicating the outcome of the surgical procedure., Results: The median duration of the surgery was 90 min. A laparotomy conversion was required in one case due to bleeding. Fluorescence was obtained in 10/12 (83.3%) patients by means of subcutaneous/perilesional injection in six of the patients, and intravenously in the other four. Hospitalization had a mean duration of three days. There were no major postoperative complications. FGLLB was used in seven patients to follow lymphoproliferative disease progression, and in five patients to establish a diagnosis. In all cases, FGLLB provided the information necessary for the correct diagnosis., Conclusions: Fluorescence with ICG offers a simple and safe method for detecting pathological lymph nodes. FGLLB in suspected intra-abdominal lymphoma can largely benefit from this new opportunity which has not yet been tested to date. Further studies with large case series are needed to confirm its efficacy., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Endometrial cancer is an emerging disease with an increase in prevalence of aggressive histotypes in recent years., Background: In the present study, potential histopathological and immunohistochemical prognostic markers were investigated. Consecutive cases of high-grade non-endometrioid carcinoma (HG-NEC) of the endometrium were considered., Methods: Each surgical specimen was routinely processed; the most significant block was selected for immunohistochemistry and tested for ER, PR, ki67, p53, E-cadherin, β-catenin, Bcl-2 and cyclin D1. For each immunomarker, the percentage of positive tumor cells was evaluated (%) and dichotomized as low and high according to the distribution in the study population. Follow-up was collected for disease-free survival (DFS) and overall survival (OS). Thirty-three cases were eligible: 19 resulted in FIGO I-II; 14 resulted in FIGO III-IV. Twelve patients suffered a recurrent disease (mean follow-up 24.6 months); 8 patients died of the disease (mean follow-up 26.6 months)., Results: Women with recurrent disease demonstrated a significantly higher Bcl2% (35.84 ± 30.96% vs. 8.09 ± 11.56%; p = 0.0032) while DOD patients had higher ki67% (75 ± 13.09% vs. 58.6 ± 19.97%; p = 0.033) and Bcl2% of border significance (34.37 ± 34.99% vs. 13 ± 17.97%; p = 0.078). As expected, FIGO III-IV had a worse DFS (HR = 3.34; 95% CI: 1.1-10.99; p = 0.034) and OS (HR = 5.19; 95% CI: 1.27-21.14; p = 0.0217). Bcl-2-high patients (Bcl2 > 10%) demonstrated a significantly worse DFS (HR = 9.11; 95% CI: 2.6-32.4; p = 0.0006) and OS (HR = 7.63; 95% CI: 1.7-34; p = 0.0084); moreover, PR low patients (PR ≤ 10%) had significantly worse DFS (HR = 3.74; 95% CI: 1.2-11.9; p = 0.02)., Conclusions: HG-NEC represents a heterogeneous group of endometrial aggressive neoplasms with a worrisome prognosis, often at an advanced stage at presentation. Bcl-2 and PR may represent promising markers to identify a subgroup of patients having an even worse prognosis requiring a careful and close follow-up.

Background/aim: Rectal cancer (RC) represents 30% of colon cancers. Despite the progress achieved in integrated chemoradiotherapy and surgical multidisciplinary treatments, the rate of local recurrence (LR) is 3.7-13%. Multivisceral resections allow many patients with pelvic recurrence to be treated in a curative manner. The purpose of this work is to assess the impact of surgery for rectal cancer patients with pelvic recurrence., Patients and Methods: In a retrospective study from 2013 to 2018, data was collected from patients who had undergone rectal resection for adenocarcinoma. We compared perioperative data, postoperative outcomes, oncological results, and survival rates., Results: 106 rectal cancer patients (40-87 years old) requiring surgery were included. The local recurrence rate was 15% (15 patients). LR patients requiring intervention were nine (56%) who underwent sphincter sparing surgeries, and 6 (44%) who underwent surgeries with sphincter resection. There was no statistically significant difference (p=0.416) in the 5-year overall survival rate of patients without recurrence compared to those with pelvic recurrence., Conclusion: Curative surgery for local recurrence from rectal cancer is safe and feasible and should be considered in selected cases as it seems to provide acceptable surgical and oncological outcomes., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The reiteration of surgical cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients affected by recurrent peritoneal metastases is still questioned regarding safety and effectiveness. This study evaluates the safety, efficacy, and associated factors of iterative CRS combined with HIPEC. This multicentric retrospective study collected data from four surgical oncology centers, on iterative HIPEC. We gathered data on patient and cancer characteristics, the peritoneal cancer index (PCI), completeness of cytoreduction (CC), postoperative complications, and overall survival (OS). In the study period, 141 CRS-plus-HIPECs were performed on 65 patients. Nine patients underwent three iterative procedures, and one underwent five. No increased incidence of complications after the second or third procedure was observed. Furthermore, operative time and hospitalization stay were significantly shorter after the second than after the first procedure ( p < 0.05). Optimal cytoreduction was achieved in more than 90% of cases in each procedure, whether first, second, or third. A five-year (5 y) OS represented 100% of the cases of diffuse malignant-peritoneal-mesotheliomas, 81.39% of pseudomyxoma peritonei, 34.67% of colorectal cancer (CRC), and 52.50% of ovarian cancer. During the second CRS combined with HIPEC, we observed a lower rate of complete cytoreduction and a non-significantly better survival in cases with complete cytoreduction (5 y-OS CC-0 56.51% vs. 37.82%, p = 0.061). Concomitant hepatic-CRC-metastasis did not compromise the CRS-plus-HIPEC safety and efficacy. This multicentric experience encourages repeated CRS-plus-HIPEC, showing promising results., Competing Interests: The authors declare no conflicts of interest.

Background and Objectives: To assess the safety and efficacy of single-port laparoscopic cholecystectomy (SPLC) for the treatment of symptomatic cholelithiasis in different gallbladder pathologic conditions., Methods: All patients who underwent SPLC in our department between October 1, 2017 and March 31, 2020 were registered consecutively in a prospective database. Patients' charts were retrospectively divided according to histological diagnosis: normal gallbladder (NG) (n = 13), chronic cholecystitis (CC) (n =47), and acute cholecystitis (AC) (n = 10). The parameters for assessing the procedure outcome included operative time, blood loss, use of additional trocars, conversion to laparotomy, intraoperative and postoperative complications, and length of hospital stay. Patient groups were statistically compared., Results: Seventy patients underwent SPLC. Duration of surgery increased from NG (55 ± 22.7 min) to CC (70 ± 33.5 min), and to AC patients (110.5 ± 50.5 min), which is statistically significant ( P  =   .001). Postoperative complication rates were 7.6% in NG patients, 17% in CC, and 30% in AC ( P  =   .442). Length of hospitalization was shorter for NG patients (1.0 ± 0.6 days) versus CC (2.0 ± 1.1 days) and AC patients (2.0 ± 4.7 days), with statistical significance ( P  = .020). Multivariate analysis found that pathology type and the occurrence of postoperative complications were independent predictors for prolonged operative times and prolonged hospital stay, respectively., Conclusion: SPLC is feasible for acute and chronic cholecystitis with good procedural outcomes. Since SPLC technique itself can be sometimes challenging with the existing technology, its application, especially in cases of acute cholecystitis, should be done with caution. Only prospective randomized studies on this approach for acute and chronic gallbladder diseases will assess the complete reliability of this technique., (© 2022 by SLS, Society of Laparoscopic & Robotic Surgeons.)

Inflammatory myofibroblastic tumor (IMT) is a very rare subtype of sarcoma, which frequently harbor chromosomal rearrangements, including anaplastic lymphoma kinase (ALK) rearrangements (almost 50% of the IMTs) and other kinase fusions such as ROS1. ROS1 fusions are present in about 10% of IMT, almost half of the ALK-negative IMT patients. Apart from radical surgery for resectable tumors, there is no standard-of-care therapy for advanced IMTs. Nonetheless, the use of tyrosine kinase inhibitors has shown promising efficacy in IMT patients with targetable genomic alterations. We report the case of a 24-year-old patient with chemotherapy-refractory metastatic IMT harboring ROS1 kinase fusion, who experienced a significant clinical and pathological response to crizotinib. This clinical case highlights the need to assess all patients with unresectable IMTs for chromosomal abnormalities and gene mutations and address them to targeted agents as well as clinical trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Comandini, Catalano, Grassi, Pesola, Bertulli, Guadagno, Spina, Mascherini, De Cian, Pistoia and Rebuzzi.)

Background: Laparoscopic lymph node biopsy through a multi-port access (MPLB) is a well-established technique for intra-abdominal lymphoma diagnosis. The aim of the current study is to assess the feasibility and the diagnostic accuracy of the single-port laparoscopic lymph node biopsy (SPLB) in intra-abdominal lymphoma. Materials and Methods: Between October 2016 and February 2019, 15 patients underwent SPLB to rule out or to follow the progression of a lymphoma. The clinical outcome and the pathology reports were analyzed retrospectively. Results: SPLB was completed laparoscopically in all cases. The total number of biopsies performed for each procedure was sometimes multiple (median: 2; range: 1-3). Duration of surgery was 85 ± 32 minutes (range: 75-105 minutes). Length of hospitalization was 1.8 ± 0.7 days (range: 1-3 days). No major postoperative complications occurred. A cutaneous infection managed conservatively was observed in a patient. In 10 patients, SPLB was used to establish a diagnosis whereas in 5 patients it was performed to follow a progression of a lymphoproliferative disease. In 93.3% of the cases, SPLB achieved the correct diagnosis and subsequent therapeutic decisions. Conclusion: SPLB has shown good procedure and postoperative outcomes as well as a high diagnostic yield, comparable to literature data on traditional MPLB. Therefore, our results show that this approach is safe and effective and can be an equally valid option to MPLB to obtain a diagnosis or to follow the progression of a lymphoproliferative disease. Further studies are necessary to support these results before its widespread adoption.

Objectives: The aim of this retrospective study is to assess the incidence of morbidity and mortality related to cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) and to evaluate their predictors, in patients with peritoneal metastasis of ovarian origin., Methods: A retrospective multicenter study was carried out investigating results from eight Italian institutions. A total of 276 patients met inclusion criteria. Predictors of morbidity and mortality were evaluated with univariate and multivariate analysis., Results: Overall morbidity was 71.4%, and severe complications occurred in 23.9% of the sample; 60-day mortality was 4.3%. According to univariate logistic regression models, grade 3-4 morbidity was related to Peritoneal Cancer Index (PCI) (OR 1.06; 95% CI 1.02-1.09; p<0.001), number of intraoperative blood transfusions (OR 1.21; 95% CI 1.10-1.34; p<0.001), Completeness of Cytoreduction (CC) score (OR 1.68; 95% CI 1.16-2.44; p=0.006) and number of anastomoses (OR 1.32; 95% CI 1.00-1.73; p=0.046). However, at the multivariate logistic regression analysis, only the number of intraoperative blood transfusions (OR 1.17; 95% CI 1.5-1.30; p=0.004) and PCI (OR 1.04; 95% CI 1.01-1.08; p=0.010) resulted as key predictors of severe morbidity. Furthermore, using multivariate logistic regression model, ECOG score (OR 2.45; 95% CI 1.21-4.93; p=0.012) and the number of severe complications (OR 2.16; 95% CI 1.03-4.52; p=0.042) were recorded as predictors of exitus within 60 days., Conclusions: The combination of CRS and HIPEC for treating peritoneal metastasis of ovarian origin has acceptable morbidity and mortality and, therefore, it can be considered as an option in selected patients., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2020 Antonio Macrì et al., published by De Gruyter, Berlin/Boston.)

Background and Objectives: The purpose of the investigation was to compare clinical results and diagnostic accuracy for conventional multiport laparoscopic lymph node biopsy (MPLB) and single-port laparoscopic lymph node biopsy (SPLB) operations at a single institution., Methods: A set of 20 SPLB patients operated on from October 2016 to May 2019 were compared to an historical series of 35 MPLB patients. Primary endpoints were the time of surgery, estimated blood loss, surgical conversion, length of stay and morbidity. The secondary endpoint was the diagnostic accuracy of the technique., Results: SPLB was completed laparoscopically in all cases. Two MPLB patients (5.7%) experienced a surgical conversion due to intraoperative difficulties. Duration of surgery was similar in SPLB and MPLB groups respectively (84 ± 31.7 min vs. 81.1 ± 22.2; P = .455). A shorter duration of hospital stay was shown for patients operated on by SPLB compared to the MPLB group (1.7 ± 0.9 days vs. 2.1 ± 1.2 days; P  =   .133). The postoperative course was uneventful in both groups. In 95% of the SPLB and 97.1% of the MPLB cases respectively, LLB achieved the necessary information for the diagnosis., Conclusion: SPLB has shown good procedural and postoperative outcomes as well as a high diagnostic yield, comparable to traditional MPLB. Therefore, our results show that this approach is safe and effective and can be an equally valid option to MPLB to obtain a diagnosis or to follow the progression of a lymphoproliferative disease. Further studies are necessary to support these results before its widespread adoption., Competing Interests: Conflicts of Interest: The authors declare no conflicts of interest., (© 2020 by JSLS, Journal of the Society of Laparoscopic & Robotic Surgeons.)

Background/aim: Leiomyosarcoma is an extremely rare, small bowel neoplasm (2% of all gastrointestinal tumours). Early diagnosis is challenging due to the slow growth of the cancer. The biological behaviour of this group of tumours is aggressive, and the first-line treatment is surgical resection., Patients and Methods: This is a report of 4 cases of small bowel leiomyosarcoma that were treated in the last ten years at Hospital San Martino: one involving the jejunum and three involving the ileum (age range=69-86 years). Three patients underwent surgical resection and one was treated with chemotherapy., Results: All patients who were eligible for surgery underwent radical resection with R0 margins. Mean overall survival was 33 months (range=8-84 months)., Conclusion: Specific guidelines for small bowel leiomyosarcoma do not currently exist and these rare cases should be discussed in a multidisciplinary context. The first treatment approach is surgery, and in some cases, multivisceral resection may be needed to obtain free margins, even in recurrent cases., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The aim of this study is to assess the morbidity and mortality related to cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colo-rectal carcinomatosis. A retrospective multi-institutional study from seven Italian Centers was performed. One hundred and seventy-two patients, submitted to cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) to treat carcinomatosis of colorectal origin, were recorded. Postoperative morbidity was evaluated in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Post-operative mortality was evaluated as patients' death within 60 days from surgical procedures. Predictors of morbidity were evaluated with univariate and multivariate analyses. Post-operative morbidity occurred in 83 patients (48.3%): grades 1-2 in 29 cases (16.9%), and grades 3-4 in 54 (31.4%). Mortality occurred in four cases (2.3%). Number of anastomoses (OR 1.45; 95% CI 1.05-2.00; p = 0.024), number of blood transfusions (OR 1.31; 95% CI 1.11-1.54; p = 0.001) and chemotherapy regimen [Oxaliplatin (OX): OR 2.87; 95% CI 1.22-6.75; p = 0.015] remained, in multivariate analysis, in a statistically significant correlation with overall morbidity. The only variable that was proven to have statistically significant correlation with 3-4 morbidity was the number of blood transfusions (OR 1.25; 95% CI 1.07-1.46; p = 0.005). Morbidity and mortality do not preclude the use of CRS plus HIPEC in the treatment of peritoneal carcinomatosis of colorectal origin.

Inferior vena cava (IVC) involvement in retroperitoneal malignancies is a rare occurrence and radical surgery with major vascular resection represents the only potential curative treatment. IVC replacement after resection is still controversial and only small series and few prospective data are available. We report a series of three patients affected by retroperitoneal masses involving IVC treated with vena cava resection without replacement. All patients were treated by a radical R0 surgical procedure associated with infrarenal IVC resection and no reconstruction. Based on preoperative radiologic imaging and intraoperative findings, one patient also underwent right nephrectomy, while another patient underwent left renal vein ligation without nephrectomy. Neither early nor late severe post-operative complications related to the absence of IVC outflow were observed. Resection without replacement of the infrarenal IVC results in acceptable morbidity, thus specific risks related to the use of prosthetic grafts can be avoided., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2019.)

Background: The incidence of trocar site hernia (TSH) in single-port laparoscopic cholecystectomy (SPC) is still a debated issue. Aim of this retrospective study was to compare the incidence of postoperative hernia and cosmetic results among patients undergoing SPC and multiport laparoscopic cholecystectomy (MPC) performed at a single institution. Methods: A series of 60 SPC and 60 MPC patients operated on between July 2016 and May 2018 were compared. Primary endpoint was to assess the incidence of TSH at long term. All the patients were admitted as outpatients for physical examination and scar measurement. Secondary endpoints were the cosmetic results assessed by a cosmesis score (CS) and the body image questionnaire (BIQ). Results: After a median 18-month follow-up (range: 6-29 months), a hernia in umbilical trocar site was detected in 4 (7.1%) SPC patients and 1 (2%) MPC patient, the difference not being statistically significant ( P  = .216). BIQ was almost equivalent in SPC and MPC groups (5.15 versus 5.27; P  = .518), respectively. Statistically significant differences in favor of SPC were found in CS (22.3 versus 19.72; P  = .001) and in total length of scars (1.2 cm versus 4 cm; P  < .001). Conclusions: SPC technique has proved to be safe and effective in experienced hands. Superior cosmesis of SPC over MPC is confirmed, but close attention to fascial closure is a vital component of SPC, and surgeons performing single-site surgery need to be aware of this increased potential for hernia formation.

Peritoneal carcinomatosis (PC) is a rare disease defined as diffused implantation of neoplastic cells in the peritoneal cavity. This clinical picture occurs during the evolution of peritoneal tumors, and it is the main cause of morbidity and mortality of patients affected by these pathologies, though cytoreductive surgery with heated intra-peritoneal chemotherapy (CRS/HIPEC) is yielding promising results. In the present study, we evaluated whether the tumor microenvironment of low-grade and high-grade PC could affect the phenotypic and functional features and thus the anti-tumor potential of NK cells. We show that while in the peritoneal fluid (PF) of low-grade PC most CD56dim NK cells show a relatively immature phenotype (NKG2A+KIR-CD57-CD16dim), in the PF of high-grade PC NK cells are, in large majority, mature (CD56dimKIR+CD57+CD16bright). Furthermore, in low-grade PC, PF-NK cells are characterized by a sharp down-regulation of some activating receptors, primarily NKp30 and DNAM-1, while, in high-grade PC, PF-NK cells display a higher expression of the PD-1 inhibitory checkpoint. The compromised phenotype observed in low-grade PC patients corresponds to a functional impairment. On the other hand, in the high-grade PC patients PF-NK cells show much more important defects that only partially reflect the compromised phenotype detected. These data suggest that the PC microenvironment may contribute to tumor escape from immune surveillance by inducing different NK cell impaired features leading to altered anti-tumor activity. Notably, after CRS/HIPEC treatment, the altered NK cell phenotype of a patient with a low-grade disease and favorable prognosis was reverted to a normal one. Our present data offer a clue for the development of new immunotherapeutic strategies capable of restoring the NK-mediated anti-tumor responses in association with the CRS/HIPEC treatment to increase the effectiveness of the current therapy.

Introduction: Uterine leiomyosarcomas (ULMS) account for 1% of all uterine malignancies and for 30% of all uterine sarcomas. The preoperative diagnosis of ULMS is challenging for the physicians, as the symptoms of these tumors are often vague and nonspecific. Moreover, as ULMS have an aggressive biologic behavior, affected women frequently have very poor prognosis., Areas Covered: The aim of this review is to describe the current pharmacotherapy for ULMS, including the ongoing clinical trials., Expert Opinion: Surgery is the standard treatment for patients with early-stage ULMS. In this setting, the role of adjuvant therapies is still unclear. In the case of advanced, persistent, or recurrent ULMS, chemotherapy is the standard care with the most frequently used drug being doxorubicin. As the outcomes for patients with the currently available conventional single or combined regimens are far from being satisfactory, new alternative and innovative medical compounds have or are being evaluated. Recently, pazopanib, and olaratumab, two innovative targeted drugs, have been approved by the Food and Drug Administration (FDA) for treating advanced soft-tissue sarcoma, including ULMS. However, further clinical investigations into new and innovation therapeutic options are warranted.

Introduction: Endometrial cancer (EC) is the most common neoplasm of the female genital tract in developed countries. Despite the progress in early detection and treatment, a significant number of cases of advanced ECs are still diagnosed. These patients have few treatment options and a poor prognosis. Our understanding of EC pathogenesis and progression has been enhanced by recent genomic studies. Among the relevant biological pathways, phosphatidylinositol 3-kinase/AKT (PIK3/AKT)-mammalian target of rapamycin (mTOR) signaling is frequently upregulated in this cancer., Areas Covered: This review covers investigational EC therapeutics acting on the PI3K/AKT/mTOR pathway. The authors review the results of clinical studies and highlight ongoing trials., Expert Opinion: Several new agents are under evaluation for treating patients with metastatic, recurrent, and persistent EC. Clinical trials investigating PI3K/AKT/mTOR inhibitors have yielded controversial results. In the near future, new studies with dual inhibitors or multi-pathways inhibitors as mono or combination therapies with conventional chemotherapy (CT) or other targeted drugs may provide more promising data. Moreover, the evaluation of new serum and histological biomarkers is an attractive strategy for patient selection.

Paraganglioma is one of the rarest neoplasms involving the ovary, with only 10 previous reports. We present a case of peritoneal carcinomatosis from primary ovarian paraganglioma and a systematic review of the literature. Clinical information was retrieved from medical records, and a systematic review of the literature was performed according to meta-analysis of observational studies in epidemiology guidelines. A 33-year-old woman presented with a 12-month history of hypertension and weight loss. She was diagnosed with ovarian paraganglioma and was treated with extensive debulking surgery to no residual disease after three cycles of neoadjuvant chemotherapy. She recurred after 6 months and was started on somatostatin-analogue. Following further disease progression with bone metastasis (treated with palliative radiotherapy), a trial with Sunitinib was started. The patient died 30 months after initial diagnosis. Of the cases reported to date, only one had peritoneal metastasis at presentation but none of them had such an ominous prognosis. Ovarian paraganglioma is an extremely rare condition. We report the first case of primary malignant ovarian paraganglioma with an exceptionally aggressive behavior. Clinicopathological correlation with immunohistochemistry is essential to avoid misdiagnosis. A standard treatment is not recommended yet but cytoreductive surgery seems to be a favorable approach to prolong survival., (© 2018 Japan Society of Obstetrics and Gynecology.)

Background: Data regarding management of former bariatric operations after onset of a malignancy are still lacking and there is no consensus whether bariatric surgery negatively influences the oncologic management of patients., Objectives: To investigate the strategy by which patients previously submitted to bariatric surgery were managed after diagnosis of malignancy of the digestive apparatus, whether a revision was performed or not, to assess the incidence of nutritional complications, and the effect of revision versus no revision of bariatric surgery on the outcome of cancer treatment., Setting: University Hospital, Italy., Methods: Occurrence of a malignancy of the digestive apparatus in patients submitted to biliopancreatic diversion was investigated retrospectively. Patients' data were collected preoperatively, at 2 and 3 years after the operation, at oncologic diagnosis, and at the longest available postoncologic follow-up., Results: From May 1976 to January 2017, 3341 morbidly obese patients were submitted to biliopancreatic diversion. Sixteen patients were diagnosed with a malignancy involving the digestive apparatus 5 to 28 years after bariatric surgery. Of 10 patients diagnosed with colorectal cancer, 6 were revised. At 2 years after biliopancreatic diversion, body mass index, hemoglobin, and iron levels were significantly lower than preoperatively. Serum transferrin and total protein were unchanged. There was no difference between body mass index, hemoglobin, transferrin, and total protein levels at 2 years and at oncologic diagnosis, or between revised and unrevised patients., Conclusion: Revision of a preexisting bariatric operation after digestive cancer surgery is common, although selected, unrevised cases do not seem to be associated with worse outcome., (Copyright © 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Obesity is associated with NAFLD, and bariatric surgery has significant impact on this liver disease, with reported improvement in hepatic fibrosis., Aims: To investigate the effects of bariatric surgery on long-term liver disease-related outcome in obese patients with nonalcoholic fatty liver disease (NAFLD) and significant liver damage., Methods: This study included 56 NAFLD patients who underwent bilio-pancreatic diversion for morbid obesity and who had significant fibrosis at intraoperative liver biopsy. Data were analyzed at 1, 3, and 5 years of follow-up, and at the latest available visit in patients who had longer follow-up. We assessed the incidence of clinically relevant liver events (ascites, hepatic encephalopathy, portal hypertension-related bleeding, and jaundice) as well as modifications of a validated biochemical index such as the NAFLD score., Results: During a median follow-up of 78 months, median weight decreased from 119 to 78 kg (P < 0.0001), and median body mass index decreased from 45.2 to 29.0 kg/m 2 (P < 0.0001). None of the patients developed clinical complications of liver disease, and none died due to liver-related causes. Median NAFLD score significantly decreased (P = 0.0005) during follow-up from - 0.929 (- 1.543 to - 0.561) to - 1.609 (- 2.056 to - 1.102). The NAFLD score category was unchanged in 32 patients (57%), improved in 18 (32%), and worsened in 6 (11%)., Conclusions: Patients with NAFLD and proven histological liver damage at surgery do not develop complications of liver disease in long term after bilio-pancreatic diversion. Moreover, noninvasive parameters of liver damage improve. Thus, preexisting liver damage does not seem to be a contraindication to bilio-pancreatic diversion.

Ovarian cancer (OC) remains relatively rare, although it is among the top 4 causes of cancer death for women younger than 50. The aggressive nature of the disease and its often late diagnosis with peritoneal involvement have an impact on prognosis. The current scientific literature presents ambiguous or uncertain indications for management of peritoneal carcinosis (PC) from OC, both owing to the lack of sufficient scientific data and their heterogeneity or lack of consistency. Therefore, the Italian Society of Surgical Oncology (SICO), the Italian Society of Obstetrics and Gynaecology, the Italian Association of Hospital Obstetricians and Gynaecologists, and the Italian Association of Medical Oncology conducted a multidisciplinary consensus conference (CC) on management of advanced OC presenting with PC during the SICO annual meeting in Naples, Italy, on September 10-11, 2015. An expert committee developed questions on diagnosis and staging work-up, indications, and procedural aspects for peritonectomy, systemic chemotherapy, and hyperthermic intraperitoneal chemotherapy for PC from OC. These questions were provided to 6 invited speakers who answered with an evidence-based report. Each report was submitted to a jury panel, representative of Italian experts in the fields of surgical oncology, gynecology, and medical oncology. The jury panel revised the reports before and after the open discussion during the CC. This article is the final document containing the clinical evidence reports and statements, revised and approved by all the authors before submission.

Octreotide and lanreotide, the first-generation somatostatin analogs, successfully control hormone hyperproduction, and related syndromes, in patients with acromegaly and neuroendocrine tumors. However, their anti-tumor effect, rather evident in large number of pituitary adenomas in acromegalic patients, has been hypothesized for a long time in patients with neuroendocrine tumors as well, although a significant tumor shrinkage has rarely been observed. However, the recent publication of the CLARINET study has strengthened the evidence, already emerged with the PROMID trial, that the long-term treatment with the first-generation long-acting somatostatin analogs may exert an anti-tumor activity on G1 and G2 enteropancreatic neuroendocrine tumors, as well. After the publication, majority of international guidelines have updated their algorithms in line with these results and this class of drugs obtained the indication as anti-tumor agents in the majority of patients with neuroendocrine tumors.

Background: Hyperthermic isolated limb perfusion (HILP) represents a limb-sparing treatment for unresectable soft tissue sarcoma (STS) of the extremities with substantial complete response rates. HILP often provides good functional limb preservation, hence a significant improvement also in terms of quality of life of the patient. Notwithstanding these clear advantages, the traditional technique is still hindered by relatively high post-operative morbidity., Method: We treated a 78-year-old female with unresectable angiosarcoma of the left leg using a new surgical approach: an entirely laparoscopic HILP., Results: No conversion from laparoscopic to "open" surgery was necessary. Since no abdominal muscle section was performed, post-operative pain was low and easily manageable; early mobilisation and early discharge were achieved. Patient developed moderate toxicity, which resolved spontaneously within 3-4 weeks, with complete return to normal daily activities after 30 d. Complete clinical response with preservation of leg function was obtained., Conclusions: We describe for the first time an entirely laparoscopic HILP. Demonstration of this technique's efficacy and safety on a large series of patients is clearly necessary but its therapeutic efficacy appears to be comparable to the standard technique. Furthermore, laparoscopic HILP has shown low post-operative morbidity: no wound complications, mild and easily manageable post-operative pain and early discharge from the hospital and early resuming of daily activities.

Background: Inguinofemoral lymphadenectomy carries a high risk of lower limb lymphedema. This report describes the feasibility of performing multiple lymphatic-venous anastomoses (MLVA) after inguinofemoral lymph node completion (LYMPHA technique) and the possible benefit of LYMPHA for preventing lymphedema., Methods: Between February, 2011 and October, 2014, 11 patients with vulvar cancer and 16 patients with melanoma of the trunk requiring inguinofemoral lymphadenectomy underwent lymph node dissection and the LYMPHA technique. Blue dye was injected into the thigh 10 min before surgery. Lymphatics afferent to the blue nodes were used to perform MLVA using a collateral branch of the great saphenous vein., Results: The mean age of patients in the vulvar cancer group was 52 years (range, 48-75 years). The melanoma group comprised seven men and nine women with a mean age of 41 years (range, 37-56 years). Of the 16 patients, 5 with vulvar cancer underwent bilateral inguinofemoral lymphadenectomy, whereas the remaining 6 patients with vulvar cancer and all 16 patients with melanoma of the trunk had unilateral node dissection. All the patients were treated by the LYMPHA technique. No lymphocele or infectious complications occurred. Transient lower-extremity edema occurred for one melanoma patient (6.25 %), which resolved after 2 months, and permanent lower-extremity edema occurred for one patient (9 %) with vulvar cancer., Conclusions: The LYMPHA technique appears to be feasible, safe, and effective for the prevention of lower limb lymphedema, thereby improving the patient's quality of life and decreasing health care costs.

Background: Filiform polyposis (FP) is an uncommon cause of non-neoplastic and non-syndromic polyposis. Several hypotheses concerning its pathogenesis have been published. FP is most frequently associated with a post-inflammatory reparative process; indeed, the most frequent association is with inflammatory bowel disease (IBD). FP is characterized by one to hundreds of uniform, slender, arborizing, vermiform projections of the large bowel mucosa and submucosa lined by normal or inflamed colonic mucosa. The most common sites for these polyps are the transverse and descending colon., Case Report: In this report we present a case of giant FP associated with locally invasive adenocarcinoma of the right colon in a 73-year-old man with no past medical history of IBD., Conclusion: Few of these cases have been reported in the literature, and out of the approximately 20 of such case reports only one other was associated with colorectal adenocarcinoma.

Aim: To assess the incidence of morbidity and mortality of Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy., Patients and Methods: A retrospective multicentric study was performed. Six hundred and eighty-three patients were recorded. Predictors of morbidity and mortality were evaluated with univariate and multivariate analysis., Results: In univariate analysis, older age, Eastern Cooperative Oncology Group score, a greater value of Peritoneal Cancer Index (PCI) and sub-optimal cytoreduction were correlated with higher mortality, while older age, presence of ascites, ovarian origin of carcinomatosis, closed technique, a greater value of PCI, longer operative time and sub-optimal cytoreduction were predictors of higher morbidity. In multivariate analysis, older age and a greater value of PCI were correlated with higher mortality; older age, ovarian origin of tumor, presence of ascites, closed technique and longer operative time were predictors of higher morbidity., Conclusion: Careful patient selection has to be performed to improve clinical outcomes., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Breast cancer-related lymphedema (LE) represents an important morbidity that jeopardizes breast cancer patients' quality of life. Different attempts to prevent LE brought about improvements in the incidence of the pathology but LE still represents a frequent occurrence in breast cancer survivors. Over 4 years ago, Lymphatic Microsurgical Preventing Healing Approach (LYMPHA) was proposed and long-term results are reported in this study. From July 2008 to December 2012, 74 patients underwent axillary nodal dissection for breast cancer treatment together with LYMPHA procedure. Volumetry was performed preoperatively in all patients and after 1, 3, 6, 12 months, and once a year. Lymphoscintigraphy was performed in 45 patients preoperatively and in 30 also postoperatively after at least over 1 year. Seventy one patients had no sign of LE, and volumetry was coincident to preoperative condition. In three patients, LE occurred after 8-12 months postoperatively. Lymphoscintigraphy showed the patency of lymphatic-venous anastomoses at 1-4 years after operation. LYMPHA technique represents a successful surgical procedure for primary prevention of arm LE in breast cancer patients., (© 2014 Wiley Periodicals, Inc.)

Cutaneous metastases of internal neoplasms are uncommon. They can be metachronous or synchronous to the primary tumor and typically appear late in the course of advanced malignant disease. Gastric cancer rarely is reported as a cause of cutaneous metastasis; the most common metastatic sites are the liver, peritoneal cavity, and lymph nodes. We report a case of cutaneous metastasis from a primary gastric tumor that had been treated 6 years prior. There was no visceral invasion. The patient was treated successfully via a relaparotomy to exclude any macroscopic abdominal recurrence and complete excision of the lesion with a plastic flap to compensate for the tissue lost in the resection. Treatment plans vary depending on the diameter and number of lesions, the presence of visceral metastases, and the physical status of the patient. Therapy generally includes local excision, irradiation, or chemotherapy.

Despite the development of minimal access dissection techniques, use of superficial groin dissection alone, and other recommendations to reduce morbidity in melanoma treatment, the incidence of lymphedema is still significant. The purpose of the current study was to assess the efficacy of microsurgical methods to limit the morbidity of inguinal lymphadenectomy. We conducted a retrospective review of patients who underwent groin dissection for melanoma treatment from February 2006 to April 2009. A total of 59 melanoma patients with positive groin lymph nodes comprised 18 patients (T-group) with melanoma in the trunk and 41 patients (E-group) who had melanoma in an extremity and currently have lymphedema. The T-group patients underwent primary prevention of lymphedema with microsurgical lymphatic-venous anastomoses (LVA) performed simultaneously with groin dissection. The E-group patients underwent LVA to treat the secondary lymphedema after an accurate oncological and lymphological assessment. Limb volume measurements and lymphoscintigraphy were performed pre- and postoperatively to assess short and long term outcome. No lymphedema occurred after microsurgical primary preventive approach in the T- group. Significant (average 80% reduction of pre-op excess volume) reduction of lymphedema resulted after microsurgical treatment for secondary leg lymphedema. Post-operative lymphoscintigraphy in 35 patients demonstrated patency of microsurgical anastomoses in all cases with an average follow-up of 42 months. Study results demonstrate that microsurgical LVA primary prevention prevented lymphedema after inguinal lymphadenectomy in the T-group patients. In addition, lymphatic-venous multiple anastomoses proved to be a successful treatment for clinical lymphedema with particular success if treated at the early stages.

Observations available for patients with acute heart failure (HF) show conflicting results, and the prognostic role of anaemia ascertained on hospital admission is not well defined. We investigated the database of the Italian Survey on Acute Heart Failure (IS-AHF) to analyze prevalence, factors associated with and the prognostic role of anaemia (defined as haemoglobin < 12 g/dl) in patients hospitalized for acute HF with either depressed or preserved (>40%) ejection fraction (EF). The median haemoglobin level of the 2,318 patients considered in this analysis was 13 g/dl (inter-quartile range 11.5-14.3). The prevalence of anaemia was 31%. Patients who had anaemia were older, more frequently female gender, hospitalized for a chronic destabilized HF, had higher prevalence of preserved EF, hyponatremia, elevated troponin and other comorbidities (including diabetes, peripheral artery disease, chronic renal failure) than those who did not have anaemia. During the hospital stay, they were treated with higher doses of diuretics, and more frequently required mechanical ventilation and ultrafiltration, and less frequently received ACEi/ARB, aldosterone blockers and beta-blockers at hospital discharge. In-hospital mortality was 12.1 and 5.3% in patients with and without anaemia, respectively (p < 0.0001). In the multivariable analysis, anaemia was a significant independent predictor of in-hospital mortality apart from age, low systolic blood pressure, impaired renal function, elevated troponin assay, the non use of beta-blocker and the requirement of inotropic drug. In conclusion, anaemia diagnosed at hospital admission for acute HF is a frequent comorbidity with meaningful implications on the clinical management and prognosis both in patients with reduced and preserved EF.

Background: L19-TNF is a tumor-targeting immunocytokine composed of the human L19 antibody binding to extra domain B (ED-B) of fibronectin of newly formed blood vessels, and of human TNF. This exploratory trial evaluates safety and clinical activity of L19-TNF plus melphalan-containing isolated limb perfusion (ILP) in extremity melanoma patients., Methods: Seven and 10 patients received 325 µg and 650 µg of L19-TNF, respectively, during the ILP. Patients were studied for safety, tolerability, and clinical activity of this experimental L19-TNF ILP procedure., Results: Non-hematologic toxicity of L19-TNF ILP was very low, but severe myelosuppression was seen in four patients. Although L19-TNF was administered at a TNF-equivalent dose of only 3.13 and 6.25% of the approved TNF (Beromun®) dose of 4 mg, L19-TNF ILP induced objective responses in 86 and 89% of patients, respectively, including a complete response (CR) in 5/10 patients treated with L19-TNF ILP at 650 µg that was durable at 12 months in four patients. No CR was seen at 325 µg of L19-TNF., Conclusions: ILP with L19-TNF had a favorable safety and a promising activity profile at a dose of 650 µg of L19-TNF, supporting the exploration of higher L19-TNF doses and a Phase II trial comparing L19-TNF ILP with standard melphalan-containing ILP., (Copyright © 2012 Wiley Periodicals, Inc.)

Background Most familial pancreatic cancer (FPC) remains unexplained. The identification of individuals with a high genetic risk of developing pancreatic adenocarcinoma (PC) is important to elucidate its biological basis and is critical to better define emerging strategies for the detection of early pancreatic neoplasms. Patients and methods A series of 225 consecutively enrolled patients with PC were tested for CDKN2A mutations. After personal and family cancer histories of all the patients had been reviewed, a subset of the patients were classified as FPC and were also tested for mutations in PALLD, PALB2, BRCA1 and BRCA2 as FPC candidate genes. Results The CDKN2A mutation rate in the 225 PC cases was 5.7%. The CDKN2A founder mutations, p.E27X and p.G101W, were predominant, but the mutation spectrum also included p.L65P, p.G67R and two novel, potentially pathogenic variants, promoter variant c.-201ACTC>CTTT and p.R144C. None of the patients with FPC harboured germline mutations in PALLD, PALB2 or BRCA2. One family was positive for the BRCA1 UV variant p.P727L. Strikingly, five of 16 patients with FPC (31%) carried CDKN2A mutations. Conclusion These findings suggest that a sizeable subset of Italian FPC families may carry CDKN2A mutations. This result may be of value for identifying the best candidates for future PC screening trials in Italy.

Purpose: To prospectively assess the efficacy of the lymphatic microsurgical preventive healing approach (LYMPHA) to prevent lymphedema after axillary dissection (AD) for breast cancer treatment., Methods: Among 49 consecutive women referred from March 2008 to September 2009 to undergo complete AD, 46 were randomly divided in 2 groups. Twenty-three underwent the LYMPHA technique for the prevention of arm lymphedema. The other 23 patients had no preventive surgical approach (control group). The LYMPHA procedure consisted of performing lymphatic-venous anastomoses (LVA) at the time of AD. All patients underwent preoperative lymphoscintigraphy (LS). Patients were followed up clinically at 1, 3, 6, 12, and 18 months by volumetry. Postoperatively, LS was performed after 18 months in 41 patients (21 treatment group and 20 control group). Arm volume and LS alterations were assessed., Results: Lymphedema appeared in 1 patient in the treatment group 6 months after surgery (4.34%). In the control group, lymphedema occurred in 7 patients (30.43%). No statistically significant differences in the arm volume were observed in the treatment group during follow-up, while the arm volume in the control group showed a significant increase after 1, 3, and 6 months from operation. There was significant difference between the 2 groups in the volume changes with respect to baseline after 1, 3, 6, 12, and 18 months after surgery (every timing P value < 0.01)., Conclusions: LYMPHA represents a valid technique for primary prevention of secondary arm lymphedema with no risk of leaving undetected malignant disease in the axilla.

Apoptosis and myostatin are major mediators of muscle atrophy and might therefore be involved in the wasting of uremia. To examine whether they are expressed in the skeletal muscle of patients with chronic kidney disease (CKD), we measured muscle apoptosis and myostatin mRNA and their related intracellular signal pathways in rectus abdominis biopsies obtained from 22 consecutive patients with stage 5 CKD scheduled for peritoneal dialysis. Apoptotic loss of myonuclei, determined by anti-single-stranded DNA antibody and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays, was significantly increased three to fivefold, respectively. Additionally, myostatin and interleukin (IL)-6 gene expressions were significantly upregulated, whereas insulin-like growth factor-I mRNA was significantly lower than in controls. Phosphorylated JNK (c-Jun amino-terminal kinase) and its downstream effector, phospho-c-Jun, were significantly upregulated, whereas phospho-Akt was markedly downregulated. Multivariate analysis models showed that phospho-Akt and IL-6 contributed individually and significantly to the prediction of apoptosis and myostatin gene expression, respectively. Thus, our study found activation of multiple pathways that promote muscle atrophy in the skeletal muscle of patients with CKD. These pathways appear to be associated with different intracellular signals, and are likely differently regulated in patients with CKD.

Background: The purpose of this manuscript is to assess the efficacy of direct lymphatic venous microsurgery in the prevention of lymphedema following axillary dissection for breast cancer., Methods: Nineteen patients with operable breast cancer requiring an axillary dissection underwent surgery, carrying out LVA between the blue lymphatics and an axillary vein branch simultaneously. The follow-up after 6 and 12 months from the operation included circumferential measurements in all cases and lymphangioscintigraphy only in 18 patients out of 19 cases., Results: Blue nodes in relation to lymphatic arm drainage were identified in 18/19 patients. All blue nodes were resected and 2-4 main afferent lymphatics from the arm could be prepared and used for anastomoses. Lymphatic-venous anastomoses allowed to prevent lymphedema in all cases. Lymphangioscintigraphy demonstrated the patency of microvascular anastomoses., Conclusions: Disruption of the blue nodes and closure of arm lymphatics can explain the significantly high risk of lymphedema after axillary dissection. LVA proved to be a safe procedure for patients in order to prevent arm lymphedema.

To examine if uremia influences muscle interleukin-6 (IL-6) metabolism we studied the exchange of IL-6 across the forearm in 16 patients with chronic kidney disease (CKD) (stages 3 and 4), in 15 hemodialysis (HD)-treated end-stage renal disease (ESRD) patients (n=15), and in six healthy controls. In addition, we performed an analysis of both IL-6 protein and IL-6 mRNA expression in muscle of CKD (stage 4) patients showing evidence of inflammation and in controls. A release of IL-6 from the forearm was observed in patients with elevated IL-6 plasma levels. Arterial IL-6 was directly related to released IL-6 (r=0.69; P<0.004) in HD patients. Both IL-6 protein and IL-6 mRNA expression were increased in muscle of inflamed CKD patients vs controls (P<0.05). Although muscle net protein balance was similar in all patients, it was significantly more negative in HD patients with high than in those with low IL-6 plasma levels (P<0.05). In addition, net protein balance was related to the forearm release of IL-6 in HD patients only (r=0.47; P<0.038). These data demonstrate that IL-6 expression is upregulated in muscle, and that muscle tissue, by releasing this cytokine, may contribute to the inflammatory response in HD patients. The release of IL-6 from peripheral tissues is associated with an increase in muscle protein loss in HD patients, suggesting that muscle release of IL-6 is linked to protein catabolism in these patients. The release of IL-6 from peripheral tissues may act as a signal for the inflammatory response and contribute to functional dysregulation in uremia.

Cryotherapy allows the destruction of unresectable liver malignancies. The abdominal approach is uneasy for recurrent colorectal metastases located in the upper part of the liver and close to the inferior vena cava, the hepatic veins and the diaphragm. A transpleurodiaphragmatic access was employed. From 1999 to 2003, ten patients with recurrent colorectal liver metastases underwent transdiaphragmatic cryotherapy via a right thoracotomy. Median diameter was 30 mm. One to 4 cryoprobes were used, depending on the size and location of the metastasis. There were no operative deaths, and only 3 patients developed minor complications. Computerized tomography examination of the liver performed one week, three months after cryotherapy, assessed treatment completeness in all patients. At 14 months, 9 patients were alive and 6 were disease-free. Two patients had liver recurrences outside the cryolesion. A transthoracic access may represent the safest and easiest surgical approach for liver tumor cryoablation in selected patients with non resectable recurrent metastases of the upper liver.

Background: Hospital admissions for heart failure are common and readmission rates are high. Many admissions and readmissions may be avoidable, so that alternative strategies are needed to improve long-term management., Methods: We conducted a randomized trial of the effect of a guideline-based intervention on rates of readmission within 90 days of hospital discharge and costs of care for patients who were hospitalized due to decompensated heart failure. The intervention consisted of comprehensive education of the patient and family, a prescribed diet and intensive application of guidelines' recommendations on pharmacological therapy. The intervention started before discharge and continued thereafter with follow-up visits for up to 3 months. Two hundred and nine guideline-managed patients were compared to 209 concurrent normally-discharged patients., Results: Patients in the study group were more prescribed beta-blockers, ACE-inhibitors, angiotensin receptor blockers, and spironolactone. Sixteen patients (8%) in the intervention group and 31 (15%) among controls were readmitted for DRG 127, within 3 months of discharge (Fisher's exact test, p < 0.01), while the 6-month mortality rate was similar between groups (9 and 11.5% respectively). Quality of life significantly improved from 5.6 +/- 1.0 to 6.1 +/- 1.9 (Mann-Whitney U-test, p < 0.05). The overall costs of care were lower for guideline-managed patients (110 vs 150 Euro per patient per month), due to the lower readmission rates., Conclusions: Our study showed that a guideline-based management program for patients with heart failure at discharge improves quality of life and reduces readmission for DRG 127 and total bed days, allowing relevant cost savings.

Background: Hospital admissions for heart failure are common and readmission rates are high. Many admissions and readmissions may be avoidable, so that alternative strategies are needed to improve long-term management., Methods: We conducted a randomized trial of the effect of a guideline-based intervention on rates of readmission within 90 days of hospital discharge and costs of care for patients who were hospitalized due to decompensated heart failure. The intervention consisted of comprehensive education of the patient and family, a prescribed diet and intensive application of guidelines' recommendations on pharmacological therapy. The intervention started before discharge and continued thereafter with follow-up visits for up to 3 months. Two hundred and nine guideline-managed patients were compared to 209 concurrent normally-discharged patients., Results: Patients in the study group were more prescribed beta-blockers, ACE-inhibitors, angiotensin receptor blockers, and spironolactone. Sixteen patients (8%) in the intervention group and 31 (15%) among controls were readmitted for DRG 127, within 3 months of discharge (Fisher's exact test, p < 0.01), while the 6-month mortality rate was similar between groups (9 and 11.5% respectively). Quality of life significantly improved from 5.6 +/- 1.0 to 6.1 +/- 1.9 (Mann-Whitney U-test, p < 0.05). The overall costs of care were lower for guideline-managed patients (110 vs 150 Euro per patient per month), due to the lower readmission rates., Conclusions: Our study showed that a guideline-based management program for patients with heart failure at discharge improves quality of life and reduces readmission for DRG 127 and total bed days, allowing relevant cost savings.

Background: This retrospective study was conducted to assess the safety, efficacy, and long-term results of neoadjuvant chemotherapy and cryotherapy as additional means for eradicating liver metastases from colorectal carcinoma when curative treatment was not possible by resection alone., Methods: Between January 1996 and December 1997, 131 patients with unresectable liver metastases were referred to our department and received chemotherapy. After 3-6 months of chemotherapy, curative surgery of liver metastases was considered possible in 57 patients, either by resection alone in 33 patients (25%) or cryotherapy associated with resection in 24 patients (18%). Characteristics and survival of patients in the cryotherapy plus resection group were compared with those of the 33 patients in the resection group., Results: All patients in the resection group had partial response to neoadjuvant chemotherapy. In the cryotherapy plus resection group, neoadjuvant chemotherapy resulted in 13 partial responses, 9 stable diseases, and 2 disease progressions. The rate of postoperative complications in the entire series was 14%. No major difference was seen between the two groups. After a median follow-up of 48 months, the median survival time was 39 months. The survival rates at 1, 3, and 4 years were similar in both groups: 94, 58, and 37% in the resection group and 92, 50, and 36% in the cryotherapy plus resection group, respectively., Conclusions: The combination of neoadjuvant chemotherapy, cryotherapy, and liver resection constitutes a promising treatment strategy for patients with extremely advanced metastatic liver involvement. Patients having more than four liver metastases from a colorectal carcinoma or patients with a poor liver reserve due to previous resection should be screened carefully to determine whether they could be candidates for this procedure., (Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10973)

Fractionated doses have been advocated to prevent chemoperitonitis after intraperitoneal infusion of mitoxantrone. Patients with peritoneal carcinomatosis of various origin underwent surgery, including intestinal resections, with minimal residual disease. Peritoneal mitoxantrone in 1000 ml/m(2) saline was planned on the first post-operative day in groups of four patients (5 mg/m(2) for 3 and 5 days, 7.5 mg/m(2) for 3 and 4 days, 10 mg/m(2) for 2-4 days, if possible). Due to dose-limiting myelosuppression, only one and three patients received the 7.5-mg 4-day and 10-mg 3-day regimens, respectively. A total of 20 patients were consequently treated. Neither major complications nor severe pain were observed. Pharmacokinetics were completed on the 1st day in five 5-mg and five 10-mg patients, on the 5th day in three 5-mg patients, and on the 3rd day in one 10-mg patient. On the 1st day, mean peritoneal peak concentrations of mitoxantrone resulted 1.45 +/-0.56 (range 0.48-1.9) and 1.9+/-0.85 (range 1.27-3.13) microg/ml in the 5-mg and 10-mg patients, respectively. Mean dialysate/plasma exposure (AUC) ratio was 115. Even in patients with sutures, early post-operative fractionated intraperitoneal mitoxantrone appears feasible and safe, with a high local advantage, for up to 5 days of treatment and a maximum tolerated total dose of 20-25 mg/m(2)., (Copyright Harcourt Publishers Limited.)

Background: The presence of liver metastases represents an independent poor risk prognostic factor for survival in patients with germ cell tumors., Methods: The clinical files of 37 patients who had undergone liver resection for the treatment of disseminated germ cell tumors were reviewed to define the indications for resection of residual liver metastases after chemotherapy in patients with germ cell tumors. The histologic patterns of primary tumor and residual disease were compared. The prognostic factors for survival were studied by univariate analysis., Results: All but 2 of 37 patients underwent complete resection. One patient died of postoperative complications. Thirteen complications occurred in 10 patients. Twelve patients had active residual tumor, 7 patients had mature teratoma, and 18 patients had only necrosis on histologic examination. Twenty-three of 37 patients (62%) were alive with no evidence of disease after a median follow-up of 66 months (range, 31-134 months). Three prognostic factors were found to be significant in the univariate analysis for unfavorable outcome: the presence of pure embryonal carcinoma in the primary tumor, liver metastases measuring > 30 mm in greatest dimension at the time of surgery, and the presence of viable, active residual disease., Conclusions: Because it is impossible to determine the histologic pattern of residual liver masses after chemotherapy with current imaging tools and percutaneous biopsy, patient selection for liver surgery may be undertaken according to the size of residual liver masses. Patients with masses that measure < or = 10 mm in greatest dimension should be considered for close follow-up, because they have a high probability of necrosis and are at low risk for malignant disease. Male patients with masses that measure > or = 30 mm in greatest dimension represent a high-risk group of patients who are not likely to benefit from liver surgery. Only male patients with masses that measure 10-29 mm in greatest dimension and all female patients with masses that measure > 10 mm in greatest dimension should be considered for liver resection., (Copyright 2001 American Cancer Society.)

Background: The aim of the study was to evaluate the results of cryosurgery in patients with multiple (five or more), heavily pretreated, unresectable liver metastases., Materials and Methods: Nineteen patients with multiple unresectable liver metastases were entered into a prospective nonrandomized trial. The liver tumours were treated during surgery under ultrasound guidance. All the patients were followed-up to assess complications, treatment response and sites of recurrence., Results: 140 metastases were identified in 19 patients (mean, 7; range, 5-25) and 13 patients had a synchronous liver resection. Cryosurgery was used to treat 90 metastases (mean diameter, 30 mm; range, 10-135). There were no treatment-related deaths and the overall rate of complications was 21%. During a mean follow-up of 28 months (range, 5-60), tumours recurred at the site of cryosurgery in two patients (10%), in the remaining liver in nine patients (47%) and elsewhere in five patients (26%). Three patients had no evidence of disease 48, 50 and 60 months after liver cryosurgery, respectively., Conclusion: Cryosurgery may be effective in the treatment of patients with multiple unresectable liver metastases and should be investigated in multimodality treatment programmes.

Desmoid tumors (DTs) are frequently associated with either surgical trauma, like scars, or physiologic trauma, like pregnancy. A DT arising in a cesarean scar during pregnancy shows both correlations. A case of DT that grew gradually in a cesarean scar during the first trimester of a subsequent pregnancy is presented. After initial MR imaging, the lesion was biopsied and carefully monitored; immediate surgical removal was considered at any time if indicated by the follow-up results. No increase in the tumor size was observed during the following 6 months of gestation, and the lesion was extirpated with mesh replacement of the abdominal defect at the time of cesarean section., (Copyright 1999 Academic Press.)