Search

We assessed the impact of DNA damage response and repair (DDR) biomarker expressions in 222 node-positive early breast cancer (BC) patients from a previous Phase III GOIM 9902 trial of adjuvant taxanes. At a median follow-up of 64 months, the original study showed no disease-free survival (DFS) or overall survival (OS) differences with the addition of docetaxel (D) to epirubicine-cyclophosphamide (EC). Immunohistochemistry was employed to assess the expression of DDR phosphoproteins (pATM, pATR, pCHK1, γH2AX, pRPA32, and pWEE1) in tumor tissue, and their association with clinical outcomes was evaluated through the Cox elastic net model. Over an extended follow-up of 234 months, we confirmed no significant differences in DFS or OS between patients treated with EC and those receiving D → EC. A DDR risk score, inversely driven by ATM and ATR expression, emerged as an independent prognostic factor for both DFS (HR = 0.41, p < 0.0001) and OS (HR = 0.61, p = 0.046). Further validation in a public adjuvant BC cohort was possible only for ATM, confirming its protective role. Overall, our findings confirm the potential role of the DDR pathway in BC prognostication and in shaping treatment strategies advocating for an integrated approach, combining molecular markers with clinical-pathological factors.

HER2 activating mutations have emerged as oncogenic drivers and therapeutic targets in a variety of human tumors. In breast cancer, these deregulations occur at low frequency, and are mostly detected in HER2-nonamplified, metastatic disease. Preclinical evidence has clarified the role of hotspot mutations in HER2 constitutive activation, defining them as an alternative mechanism to HER2 gene amplification. Furthermore, recent clinical studies have indicated the emergence of newly acquired HER2 deregulations in significant proportions of breast cancer patients who experience disease progression following both endocrine and HER2-targeted therapies. As the involvement of HER2 mutation in therapy resistance may profoundly impact patient outcomes on successive therapies, several clinical trials are currently investigating the efficacy of various HER2-targeted drugs in HER2-mutant breast cancer. In this review, we firstly summarize the structural organization of the HER2 oncogene and its historical impact on breast cancer prognosis and therapeutic advancement. Then, we provide an overview of the frequencies and functional relevance of clinically recurrent HER2 mutations in breast cancer with a special focus on their role in therapeutic resistance. Finally, we provide a collection of the clinical trials that are currently exploring novel therapeutic approaches for this patient subset and discuss the related perspectives and challenges., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

After a failed laparoscopic adjustable gastric band (LAGB), laparoscopic sleeve gastrectomy (LSG) has been proposed as revisional surgery. Those patients that receive a second restrictive procedure fall into a small subgroup of patients with more than one restrictive procedure (MRP). If also the second restrictive procedure fails, the correct surgical strategy is a challenge for the surgeon. Roux-en-Y gastric bypass (RYGB) may be an option but there is no evidence in the literature on whether the procedure is effective in treating failures after MRP. This study aims to evaluate the influence of the previous number of restrictive interventions (MRP vs single LSG) in the results of RYGB as revisional surgery. We have retrospectively analyzed patients who underwent conversion from laparoscopic sleeve gastrectomy (LSG), or from multiple restrictive procedures (MRP), to RYGB for weight regain (WR) or insufficient weight loss (IWL) between 2009 and 2019. The number of patients analyzed was 69 with conversion to RYGB after LSG and 44 after MRP. The reduction of excess weight (%TWL) at 3, 6, 12, 24 RYGB postoperative months was respectively of 11.03%, 16.39%, 21.43%, and 24.22% in the MRP group, and of 10.97%, 16.4%, 21.22%, and 22.71% in the LSG group. No significant difference was found in %TWL terms after RYGB for the MRP group and the LSG group with an overall %TWL, which was 11.00 ± 6.03, 16.40 ± 8.08, 21.30 ± 9.43, and 23.30 ± 9.91 respectively at 3, 6, 12, and 24 months. The linear regression model highlighted a positive relationship between the %EWL post-bypass at 24 months and the time elapsed only between the LSG and RYGB in the MRP group patients ( p < 0.001). RYGB has proved to be a reliable technique with good results in terms of weight loss after failed bariatric surgery both in patients who previously underwent MRP and in those who underwent exclusively LSG. RYGB showed better results in patients who experienced WR than in those who had IWL from previous techniques.

Background: In triple negative breast cancer patients treated with neoadjuvant chemotherapy, residual disease at surgery is the most relevant unfavorable prognostic factor. Current guidelines consider the use of adjuvant capecitabine, based on the results of the randomized CREATE-X study, carried out in Asian patients and including a small subset of triple negative tumors. Thus far, evidence on Caucasian patients is limited, and no real-world data are available., Methods: We carried out a multicenter, observational study, involving 44 oncologic centres. Triple negative breast cancer patients with residual disease, treated with adjuvant capecitabine from January 2017 through June 2021, were recruited. We primarily focused on treatment tolerability, with toxicity being reported as potential cause of treatment discontinuation. Secondarily, we assessed effectiveness in the overall study population and in a subset having a minimum follow-up of 2 years., Results: Overall, 270 patients were retrospectively identified. The 50.4% of the patients had residual node positive disease, 7.8% and 81.9% had large or G3 residual tumor, respectively, and 80.4% a Ki-67 >20%. Toxicity-related treatment discontinuation was observed only in 10.4% of the patients. In the whole population, at a median follow-up of 15 months, 2-year disease-free survival was 62%, 2 and 3-year overall survival 84.0% and 76.2%, respectively. In 129 patients with a median follow-up of 25 months, 2-year disease-free survival was 43.4%, 2 and 3-year overall survival 78.0% and 70.8%, respectively. Six or more cycles of capecitabine were associated with more favourable outcomes compared with less than six cycles., Conclusion: The CaRe study shows an unexpectedly good tolerance of adjuvant capecitabine in a real-world setting, although effectiveness appears to be lower than that observed in the CREATE-X study. Methodological differences between the two studies impose significant limits to comparability concerning effectiveness, and strongly invite further research., Competing Interests: LP received speaker fees from Novartis, outside the submitted work. UDG: Pfizer, BMS, MSD, PharmaMAR, AStellas, Bayer, Ipsen, Novartis; Invited speaker Roche, BMS, SAnofi, AstraZeneca; received research grants from AstraZeneca, SAnofi, Roche, outside the submitted work. AF received honoraria as a speaker from Eli Lilly, Novartis, Pierre-Fabre, outside the submitted work. GT: advisory boards from Novartis, Pfizer, Eisai, Roche, and Eli Lilly, outside the submitted work. DS: advisory boards from Novartis, Pfizer, Eisai, Roche, and Eli Lilly, outside the submitted work. NLV: Roche, MSD, Eisai, Novartis, AstraZeneca, GSK, Pfizer, Gentili, Daiichi Sankyo, Dephaforum, outside the submitted work. OG: Eisai, MSD, Gilead, Seagen, Novartis, Eli Lilly, outside the submitted work. IM: advisory boards from Eli Lilly, Novartis, Gentili, Roche, Pfizer, Ipsen, and Pierre-Fabre, outside the submitted work. GD’A: Novartis, Amgen, Eli Lilly outside the submitted work. TG received travel grants from Eisai, Roche, Pfizer, and Novartis; speaker fees/advisory boards from Roche, Pfizer, Novartis, Gentili, and Eli Lilly, outside the submitted work. MPi Consultant/advisory boards from Gilead, Eli Lilly, Pfizer, Novartis, Gentili, MSD, outside the submitted work. RB received research grant/advisory boards from AstraZeneca, Boehringer Ingelheim, Novartis, MSD, Otsuka, Eli Lilly, Roche, Amgen, GSK, Eisai, outside the submitted work. FGi: advisory boards from Gilead, Daiichi Sankyo, Seagen, outside the submitted work. MEC consultant/advisory role for Pierre-Fabre, Roche, Novartis, Eli Lilly, Celgene, outside the submitted work. RT: AstraZeneca, Eisai, Pfizer, Eli Lilly, MSD, Exact Science, outside the submitted work. AB: MSD, BMS, Pfizer, Novartis, Roche outside the submitted work. AM received travel grants from Eisai, Celgene, and Novartis Ipsen; personal fees/advisory boards from Eisai, Novartis, AstraZeneca, Teva, Pfizer, and Celgene, outside the submitted work. IP received personal fees/advisory boards from Roche, Pfizer, Novartis, Italfarmaco, Gentili, and Pierre-Fabre. LG received congress travel accomodation from Roche, Daiichi Sankyo, AstraZeneca, Pfizer, Novartis; advisory role for Astra Zeneca outside the submitted work. MMin: Novartis, MSD, Eli Lilly, outside the submitted work. LM received personal fees/advisory board from Roche, Novartis, Eisai, and Pfizer, outside the submitted work. EC: Astellas, Roche, BMS, Jansen, MSD, Sirtex, Merck, Bayer, Servier, Novartis, outside the submitted work. PM has/had a consultant/advisory role for BMS, Roche, Genentech, MSD, Novartis, Amgen, Merck Serono, Pierre-Fabre and Incyte, outside the submitted work. PV received speaker fees/advisory boards from Roche, Pfizer, Novartis and Eli Lilly, outside the submitted work. The remaining 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 © 2023 Di Lisa, Krasniqi, Pizzuti, Barba, Cannita, De Giorgi, Borella, Foglietta, Cariello, Ferro, Picardo, Mitidieri, Sini, Stani, Tonini, Santini, La Verde, Gambaro, Grassadonia, Tinari, Garrone, Sarobba, Livi, Meattini, D’Auria, Vergati, Gamucci, Pistelli, Berardi, Risi, Giotta, Lorusso, Rinaldi, Artale, Cazzaniga, Zustovich, Cappuzzo, Landi, Torrisi, Scagnoli, Botticelli, Michelotti, Fratini, Saltarelli, Paris, Muratore, Cassano, Gianni, Gaspari, Veltri, Zoratto, Fiorio, Fabbri, Mazzotta, Ruggeri, Pedersini, Valerio, Filomeno, Minelli, Scavina, Raffaele, Astone, De Vita, Pozzi, Riccardi, Greco, Moscetti, Giordano, Maugeri-Saccà, Zennaro, Botti, Pelle, Cappelli, Cavicchi, Vizza, Sanguineti, Tomao, Cortesi, Marchetti, Tomao, Speranza, Sperduti, Ciliberto and Vici.)

The Hippo pathway and its two key effectors, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), are consistently altered in breast cancer. Pivotal regulators of cell metabolism such as the AMP-activated protein kinase (AMPK), Stearoyl-CoA-desaturase 1 (SCD1), and HMG-CoA reductase (HMGCR) are relevant modulators of TAZ/YAP activity. In this prospective study, we measured the tumor expression of TAZ, YAP, AMPK, SCD1, and HMGCR by immunohistochemistry in 65 Her2+ breast cancer patients who underwent trastuzumab-based neoadjuvant treatment. The aim of the study was to assess the impact of the immunohistochemical expression of the Hippo pathway transducers and cell metabolism regulators on pathological complete response. Low expression of cytoplasmic TAZ, both alone and in the context of a composite signature identified by machine learning including also low nuclear levels of YAP and HMGCR and high cytoplasmic levels of SCD1, was a predictor of residual disease in the univariate logistic regression. This finding was not confirmed in the multivariate model including estrogen receptor > 70% and body mass index > 20. However, our findings were concordant with overall survival data from the TCGA cohort. Our results, possibly affected by the relatively small sample size of this study population, deserve further investigation in adequately sized, ad hoc prospective studies.

The restoration of bowel continuity following Hartmann's Procedure (HP) has been reported hitherto with high morbidity and mortality rates. No clear guidelines exist about timing in Hartmann's Reversal (HR), the literature data being conflicting. We have sought to investigate the effect of the interval time between HP and HR in short- and long-term HR outcomes through a retrospective study based on consecutive patients undergoing HR between 2009 and 2017 in two regional hospitals in Italy. Demographic characteristics, comorbidities, intra- and post-operative data, as well as early complications, were recorded. Long-term data were collected on the surgical site occurrences of Incisional Ventral Hernia (IVH). One hundred and five patients were recruited for the study. Late HR, female gender, and long operating time were related to the highest incidence of peri-operative complications. Patients who developed IVH had undergone HR at significantly shorter times and had a higher Body Mass Index (BMI). The timing of HR seems to be an important variable linked to the onset of early and late post-operative complications. The patients submitted to early HR show a significantly lower complication rate but, at the same time, a higher rate of IVH incidence after restorative surgery. These data, in our opinion, reflect the need for planning, where possible, an early restoration of bowel continuity after HP.

Background: The present study aims to evaluate how the measures to contain the SARS-CoV-2 spreading affected the surgical site infections (SSIs) rate in patients who underwent nondeferrable breast cancer surgery (BCS)., Methods: This study is a retrospective analysis of prospectively collected data from a consecutive series of patients underwent nondeferrable BCS in a regional Italian Covid-free hub during two different period: March to April 2020 (pandemic cohort [PC]) and March till April 2019 (control cohort [CC]). SSIs were defined according to the criteria established by the Center for disease control and prevention (CDC) and additional treatment, serous discharge, erythema, purulent exudate, separation of deep tissues, isolation of bacteria, and stay (ASEPSIS) scoring systems., Results: One hundred ninety-nine patients were included in the present study: 100 and 99 patients who underwent nondeferrable BCS from March to April 2020 (PC) and from March to April 2019 (CC), respectively. The overall SSIs rate in this series was 9.1% according to CDC criteria and 6.5% according to ASEPSIS criteria. The SSIs incidence decreased during the pandemic period. Moreover, the SSIs rate according to ASEPSIS criteria was statistically lower in the PC than in the CC. We observed significant evidence of higher SSIs, both in terms of CDC and ASEPSIS score, in patients having undergone breast reconstruction compared with patients not undergoing immediate reconstruction., Conclusions: The restrictive measures issued during the lockdown period seemed to lower the SSIs rates in patients undergoing nondeferrable BCS., Competing Interests: The authors declare that they have no financial conflict of interest with regard to the content of this report.The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2022 The Authors. Published on behalf of the Associazione Chirurghi Ospedalieri Italiani and Wolters Kluwer.)

Background: The evolution of therapeutic landscape of human epidermal growth factor receptor-2 (HER2)-positive breast cancer (BC) has led to an unprecedented outcome improvement, even if the optimal sequence strategy is still debated. To address this issue and to provide a picture of the advancement of anti-HER2 treatments, we performed a large, multicenter, retrospective study of HER2-positive BC patients., Methods: The observational PANHER study included 1,328 HER2-positive advanced BC patients treated with HER2 blocking agents since June 2000 throughout July 2020. Endpoints of efficacy were progression-free survival (PFS) and overall survival (OS)., Results: Patients who received a first-line pertuzumab-based regimen showed better PFS ( p < 0.0001) and OS ( p = 0.004) than those receiving other treatments. Median PFS and mOS from second-line starting were 8 and 28 months, without significant differences among various regimens. Pertuzumab-pretreated patients showed a mPFS and a mOS from second-line starting not significantly affected by type of second line, that is, T-DM1 or lapatinib/capecitabine ( p = 0.80 and p = 0.45, respectively). Conversely, pertuzumab-naïve patients receiving second-line T-DM1 showed a significantly higher mPFS compared with that of patients treated with lapatinib/capecitabine ( p = 0.004). Median OS from metastatic disease diagnosis was higher in patients treated with trastuzumab-based first line followed by second-line T-DM1 in comparison to pertuzumab-based first-line and second-line T-DM1 ( p = 0.003), although these data might be partially influenced by more favorable prognostic characteristics of patients in the pre-pertuzumab era . No significant differences emerged when comparing patients treated with 'old' or 'new' drugs ( p = 0.43), even though differences in the length of the follow-up between the two cohorts should be taken into account., Conclusion: Our results confirmed a relevant impact of first-line pertuzumab-based treatment and showed lower efficacy of second-line T-DM1 in trastuzumab/pertuzumab pretreated, as compared with pertuzumab-naïve patients. Our findings may help delineate a more appropriate therapeutic strategy in HER2-positive metastatic BC. Prospective randomized trials addressing this topic are awaited., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: EK, IS, MB, MM, MMaz, EMV, IM, RB, FSDL, MP, LI, ER, NDO, ST, CF, KC, FR, AC, MAF, GB, AB, GDA, AC, AR, BTS, GS, FG, RS, DM, DC, EMC, VS, LMe, GT, MR, LM, MMi, EMR, PS, NS, LL, NT, AG, AFS, RR, MRV, EL, SS, BF, MMS, MDT, AM, AO, VL, EC, GS, PP, FC, LL, CB, FT, SC, GB, FP, FCav, OB, EF, JF, SS, and GC declare no conflicts of interest. LP received travel grants from Eisai, Roche, Pfizer, and Novartis; speaker fees from Roche, Pfizer, Novartis, and Gentili. TG received travel grants from Eisai, Roche, Pfizer, and Novartis; speaker fees/advisory boards from Roche, Pfizer, Novartis, Gentili, and Lilly. CN received travel grants/personal fees from Pfizer, Eisai, Novartis, Merck Sharp & Dohme, and AstraZeneca. EB is supported by the Italian Association for Cancer Research AIRC-IG 20583; he was supported by the International Association for Lung Cancer (IASLC), the LILT (Lega Italiana per la Lotta contro I Tumori), and Fondazione Cariverona; he received speakers’ and travels’ fee from MSD, AstraZeneca, Celgene, Pfizer, Helsinn, Eli Lilly, BMS, Novartis, and Roche; consultant’s fee from Roche, Pfizer; institutional research grants from AstraZeneca and Roche. AM received travel grants from Eisai, Celgene, and Novartis Ipsen; personal fees, advisory boards from Eisai, Novartis, AstraZeneca, Teva, Pfizer, and Celgene. IP received personal fees/advisory boards from Roche, Pfizer, Novartis, Italfarmaco, Gentili, and Pierre Fabre. LM received personal fees/advisory board from Roche, Novartis, Eisai, and Pfizer. GT and DS: advisory board Novartis, Pfizer, Eisai, Roche, and Eli Lilly. PM has/had a consultant/advisory role for BMS, Roche Genentech, MSD, Novartis, Amgen, Merck Serono, Pierre Fabre, and Incyte. PV received travel grants from Eisai, Roche, Pfizer, and Novartis; speaker fees/advisory boards from Roche, Pfizer, Novartis, Gentili, and Eli Lilly., (© The Author(s), 2021.)

The actual role of chemotherapy in vulvar cancer is undeniably a niche topic. The low incidence of the disease limits the feasibility of randomized trials. Decision making is thus oriented by clinical and pathological features, whose relevance is generally weighted against evidence from observational studies and clinical practice. The therapeutic management of vulvar cancer is increasingly codified and refined at an individual patient level. It is of note that the attitude towards evidence sharing and discussion within a multidisciplinary frame is progressively consolidating. Viable options included in the therapeutic armamentarium available for vulvar cancer patients are frequently an adaption from standards used for cervical or anal carcinoma. Chemotherapy is more frequently combined with radiotherapy as neo-/adjuvant or definitive treatment. Drugs commonly used are platinum derivative, 5-fluorouracil and mitomicin C, mostly in combination with radiotherapy for radiosensitization. Exclusive chemotherapy in the neo-/adjuvant setting comprises platinum-derivative, combined with bleomicin and methotrexate, 5-fluorouracil, ifosfamide or taxanes. In advanced disease, current regimens include cisplatin-based chemoradiation, with or without 5-fluorouracil, or doublets with platinum in combination with a taxane. Our work is also enriched by a concise excursus on the biologic pathways underlying vulvar cancer. Introductory hints are also provided on targeted agents, a rapidly evolving research field.

The Covid-19 pandemic has challenged hard the national health systems worldwide. According to the national policy issued in March 2020 in response to the evolving Covid-19 pandemic, several hospitals were re-configured as Covid-19 centers and elective surgery procedures were rescheduled according to the most recent recommendations. In addition, Covid-19 protected cancer hubs were established, including the Regina Elena National Cancer Institute of Rome, Central Italy. At our Institute, the Breast Surgery Department continued working under the sign of a multidisciplinary approach. The number of professional figures involved in case evaluation was reduced to a minimum and interactions took place in the full respect of the required safety measures. Treatments for benign disease, pure prophylactic surgery and elective reconstructive procedures were all postponed and priority was assigned to the histologically-proven malignant breast tumors and highly suspicious lesions. From March 15th though April 30th 2020, we treated a total of 79 patients. This number is fully consistent with the average quantitative standards reached by our Department under ordinary circumstances. Patients were mostly discharged the day after surgery and none was readmitted due to surgery-related late complications. More generally, post-operative complications rates were unexpectedly low, particularly in light of the relatively high number of reconstructive procedures performed in this emergency situation. A strict follow up was performed based on the close contact with the surgical staff by telephone, messaging apps and telemedicine.Patients ascertainment for their Covid-19 status prior to hospital admission and hospital discharge allowed to maintain the "no-Covid-19" status at our Institution. In addition, during the aforementioned time window, none of the care providers developed SARS-CoV-2 infection or disease, as shown by the results of anti-SARS-CoV-2 immunoglobulin M and G profiling. In conclusions, elective breast cancer surgery procedures were successfully performed in a lockdown situation due to a novel viral pandemic. The well-coordinated regional and hospital efforts in terms of medical resource re-allocation and definition of clinical priorities allowed to maintain high quality standards of breast cancer care while ensuring safety to the cancer patients and care providers involved.

Background: For patients with melanoma metastases in the pelvic and groin regions, the median survival time (MST) was 8 mo with old treatments, whereas today is approximately 20 mo with new target therapy and novel immunotherapy. Unfortunately, approximately 30% of patients are nonresponsive to these new drugs., Materials and Methods: Thirty-six patients, previously progressing after standard treatments, collectively received 146 melphalan (30 mg/m 2 ) hypoxic pelvic perfusions with hemofiltration, in association with palliative excision in most cases., Results: The median follow-up time was 15 mo. Among 36 patients, three patients were alive without evidence of disease after 62, 95, and 118 mo, respectively. Thirty-three patients died of melanoma. The overall MST was 15 mo. The 5-y survival rate was 8%. The MST was 37 mo for stage IIIB; 19 mo for stage IIIC; and 6 mo for stage IV. The MST was 11 mo for patients with ≥1 mitosis per mm 2 and 20 mo for patients with <1 mitosis per mm 2 ; 17 mo for patients who received excision and 7 mo for patients who did not receive excision; and 19.5 mo for patients who received >2 treatments and 7.5 mo for patients who received ≤2 treatments., Conclusions: Pelvic/inguinal perfusion is a safe and feasible treatment for patients with advanced melanoma. Further studies are necessary to establish if it may play a role in patients who fail current systemic therapies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Because laparoscopic cholecystectomy (LC) is widely recognized as a "mild" or "mini-invasive" kind of surgery, in this prospective nonrandomized study, we investigated the effect of intestinal manipulation on intestinal permeability and endotoxemia, in patients undergoing elective cholecystectomy by comparing the laparoscopic with the laparotomic approach., Summary Background Data: The intestine is susceptible to operations at remote locations, and the barrier function is altered during intestinal manipulation, leading to bacterial or endotoxin translocation into the systemic circulation., Methods: Forty-three patients undergoing elective cholecystectomy were divided into either the laparotomic (n = 22) or laparoscopic (n = 21) approach. Intestinal permeability was measured preoperatively and at day 1 and day 3 after surgery using the lactulose/mannitol absorption test. Serial venous blood samples were taken at 0, 30, 60, 90, 120, and 180 minutes, and at 12, 24, and 48 hours after surgery, for endotoxin measurement using the chromogenic limulus amoebocyte lysate assay., Results: Intestinal permeability was significantly increased at day 1 [0.106 +/- 0.005 (mean +/- SEM)] in the laparotomic group compared with the preoperative level (0.019 +/- 0.005, P < 0.05) and to the laparoscopic group at day 1 (0.019 +/- 0.005, P < 0.05), which showed no change in comparison with the preoperative level. A significantly higher concentration of systemic endotoxin was detected intraoperatively in the laparotomic group of patients in comparison to the laparoscopic group (P < 0.05). There was a significant positive correlation between systemic endotoxemia and intestinal permeability (r(s) = 0.958; P = 0.001)., Conclusions: An increase in intestinal permeability and a greater degree of systemic endotoxemia are observed during laparotomic cholecystectomy. This suggests that intestinal manipulation may impair gut mucosal barrier function and contribute to the systemic inflammatory response see in open cholecystectomy.

Since laparoscopic cholecystectomy (LC) is widely recognised as being a "mild" or minimally invasive kind surgery, the aim of this prospective non-randomised study was to investigate the effect of intestinal manipulation on intestinal permeability and endotoxaemia in patients undergoing elective cholecystectomy, comparing the laparoscopic and laparotomic approaches. The intestine is susceptible to operations at remote locations, and the barrier function is altered during intestinal manipulation, leading to bacterial or endotoxin translocation into the systemic circulation. Fifty-three patients undergoing elective cholecystectomy were divided into two groups on the basis of laparotomic (n = 27) or laparoscopic (n = 26) approach. Intestinal permeability was measured preoperatively, and on day 1 and day 3 after surgery using the lactulose/mannitol absorption test. Serial venous samples were taken at 0, 30, 60, 90, 120 and 180 minutes, and at 12, 24 and 48 hours after surgery, for endotoxin measurement using the chromogenic limulus amoebocyte lysate assay. Intestinal permeability was significantly increased on day 1 [0.106 +/- 0.0005 (mean +/- S.E.M.)] in the laparotomic group compared to the preoperative level (0.019 +/- 0.005, p < 0.05) and to the laparoscopic group on day 1 (0.019 +/- 0.005, p < 0.05) which showed no change in comparison with the preoperative level. A significantly higher concentration of systemic endotoxin was detected intraoperatively in the laparotomic group of patients in comparison with the laparoscopic group (p < 0.05). There was significant positive correlation between systemic endotoxaemia and intestinal permeability (rs = 0.958; p = 0.001). An increase in intestinal permeability and degree of systemic endotoxaemia are observed during laparotomic cholecystectomy. This suggets that intestinal manipulation may impair the mucosal barrier function of the gut and contribute to the systemic inflammatory response seen in open cholecystectomy.

Acute abdomen accounts for 13-40% of all emergency surgical admissions. The aim of this prospective randomised controlled study was to examine the role of early laparoscopy in the management of acute abdomen compared with the more traditional active observation approach. From July 1993 to August 2004, 522 patients consecutively admitted with acute abdomen were randomised to either early laparoscopy (260 patients) (group 1) or active observation and non-invasive investigation (262 patients) (group 2). Baseline investigations included a full blood count, a pregnancy test in women of child-bearing age, and chest and/or abdominal radiography, if indicated clinically. Sixty-two patients in the laparoscopy group underwent a total of 116 radiological investigations compared with a total of 558 investigations in all patients in the observation group (p < 0.05). In the observation group, 34.7% of patients remained without a clear diagnosis compared with 4.2% of patients in the early laparoscopy group (p < 0.0001). The morbidity rate was 1.1% in group 1 and 27% in group 2 (p < 0.0001). The duration of hospital stay was significantly shorter in group 1 (3.1 vs 7.3 days) (p < 0.01). Eight patients in group 1 required readmission (total readmission: 46 days) compared with 58 patients in group 2 with a total readmission of 201 days (p < 0.05). Early laparoscopy is valuable in the management of acute abdomen. It affords significantly higher diagnostic accuracy and a greater improvement in quality of life than the more traditional observation approach.