Comprehensive management of epithelial ovarian cancer with peritoneal metastases

Ovarian cancer has as its predominant pattern of dissemination metastases to the peritoneal surfaces and disease spread within the abdomen and pelvis that most commonly causes the patients demise. To combat peritoneal metastases, cytoreductive surgery with peritoneal and visceral resections is combined with intraperitoneal and systemic chemotherapy. Chemotherapy given in the operating room after the complete visible removal of ovarian cancer is hyperthermic intraperitoneal chemotherapy. The results of the combined treatment are determined by the extent of prior surgery, the extent of disease as established by the peritoneal cancer index, and the quality of the cytoreduction as measured by the completeness of cytoreduction score. Recent clinical information on patients with recurrent ovarian cancer suggest a median overall survival of up to 60 mo. These data are greatly improved over the one year survival observed in the past.

Cytoreductive surgery in primary advanced epithelial ovarian cancer

Epithelial ovarian cancer is one of the most common malignancy and one of the principal causes of death among gynaecological neoplasm. The majority of patients(about 70%) present with an advanced International Federation of Gynaecology and Obstetrics stage disease. The current standard treatment for these patients consists of complete cytoreduction and combined systemic chemotherapy(CT). An increasing proportion of patients undergoing complete cytoreduction to no gross residual disease(RD) is associated with progressively longer overall survival. As a counterpart, some authors hypothesized the improving in survival could be due more to a less diffused initial disease than to an increase in surgical cytoreduction rate. Moreover the biology of the tumor plays an important role in survival benefi t of surgery. It's still undefi ned how the intrinsic features of the tumor make intra-abdominal implants easier to remove.Adjuvant and hyperthermic intraperitoneal CT could play a decisive role in the coming years as the completeness of macroscopic disease removal increases with advances in surgical techniques and technology. The introduction of neo-adjuvant CT moreover will play a decisive role in the next years Anyway cytoreduction with no macroscopic residual of disease should always be attempted. However the defi nition of RD is not universal. A unique and defi nitive defi nition is needed.

Cytoreductive surgery and HIPEC after neoadjuvant chemotherapy for advanced epithelial ovarian cancer

AIM: To reduce postoperative complications and to make possible an optimal cytoreduction, neoadjuvant chemotherapy(NACT) followed by interval debulking surgery has been applied with encouraging results. METHODS: Between December 2009 and February 2012, patients with stage ⅢC-Ⅳ epithelial ovarian cancer(EOC) underwent diagnostic laparoscopy, to assess the feasibility of optimal debulking surgery. The modifi ed Fagotti score was applied to assess the feasibility of resection with zero residual tumor. Patients who were not candidate for upfront debulking surgery were submitted to NACT, then reassessed according to the RECIST 1.1 criteria and submitted to cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC) if they showed clinical response or stable disease. The remaining cycles of adjuvant systemic chemotherapy(ASCT) were administered postoperatively, to complete 6 cycles of systemic chemotherapy.RESULTS: Nine patients were included. Clinical response to NACT was complete in 3 patients and partial in 5 patients; one patient had stable disease. All patients underwent CRS resulting in CC0 disease prior to HIPEC. Average operative time was 510 min. Average intensive care unit stay was 2 d. Average postoperative hospital stay was 25 d. No postoperative mortality was observed. One patient experienced pelvic abscess. One patient refused ASCT. The remaining 8 patients started ASCT. Average time to chemotherapy was 36 d. All patients are alive, with an average follow up of 11 mo. Eight patients are disease-free at follow up.CONCLUSION: HIPEC after CRS for advanced EOC is feasible with acceptable morbidity and mortality. NACT may increase the chance for achieving complete cytoreduction. Phase 3 studies are needed to determine the effects of HIPEC on survival.

Criticalities in randomized controlled trials on HIPEC for ovarian cancer

Since the 1990 s, many oncological surgery groups around the world started to apply hyperthermic intraperitoneal chemotherapy(HIPEC) to the different peritoneal spread cancers. The rationale of the application of HIPEC after surgery is to complete the cytoreductive procedure. This combined treatment has now been successfully applied to many different intra-abdominal neoplasms. However, the treatment of peritoneal surface malignancies and the administration of HIPEC still lack high graded evidence data, especially in ovarian cancer. Experimental data exists about every step of the treatment of peritoneal spread ovarian cancer but unfortunately they have not yet been translated into phase Ⅲ clinical randomized trials. Moreover, treatment protocols differ between different centers. A systematic review of published randomized trial protocols was performed. HIPEC techniques are miscellaneous and not yet standardized. Well structured phase Ⅲ randomized trials among specialized centers are needed to investi-gate the effi cacy of this therapeutic approach, as well as technical details that may contribute to the standardization of the procedure and limit morbidity and mortality. In particular, new criteria are mandatory to uniformly stage the disease, to objectively evaluate the extension of cytoreduction and consequently the residual disease, to decide the best method of performing hyperthermia and to perfuse drugs. Moreover, pharmacokinetic and pharmacodynamic studies are urgently needed to assess the best type and dose of anticancer drugs.

Adhesive small bowel adhesions obstruction: Evolutions in diagnosis, management and prevention

Intra-abdominal adhesions following abdominal surgery represent a major unsolved problem. They are the first cause of small bowel obstruction. Diagnosis is based on clinical evaluation, water-soluble contrast followthrough and computed tomography scan. For patients presenting no signs of strangulation, peritonitis or severe intestinal impairment there is good evidence to support non-operative management. Open surgery is the preferred method for the surgical treatment of adhesive small bowel obstruction, in case of suspected strangulation or after failed conservative management, but laparoscopy is gaining widespread acceptance especially in selected group of patients. "Good" surgical technique and anti-adhesive barriers are the main current concepts of adhesion prevention. We discuss current knowledge in modern diagnosis and evolving strategies for management and prevention that are leading to stratified care for patients.

Advanced gastric cancer:what we know and what we stillhave to learn

Gastric cancer is a common neoplastic disease and, more precisely, is the third leading cause of cancer death in the world, with differences amongst geographic areas. The definition of advanced gastric cancer is still debated. Different stadiating systems lead to slightly different stadiation of the disease, thus leading to variations between the single countries in the treatment and outcomes. In the present review all the possibilities of treatment for advanced gastric cancer have been analyzed. Surgery, the cornerstone of treatment for advanced gastric cancer, is analyzed first, followed by an investigation of the different forms and drugs of chemotherapy and radiotherapy. New frontiers in treatment suggest the growing consideration for intraperitoneal administration of chemotherapeutics and combination of traditional drugs with new ones. Moreover, the necessity to prevent the relapse of the disease leads to the consideration of administering intraperitoneal chemotherapy earlier in the therapeutical algorithm.

Acute appendicitis: Epidemiology, treatment and outcomesanalysis of 16544 consecutive cases

AIM To investigate the epidemiology,treatment and outcomes of acute appendicitis(AA) in a large population study.METHODS This is a retrospective cohort study derived from the administrative dataset of the Bergamo district healthcare system(more than 1 million inhabitants) from 1997 to 2013.Data about treatment,surgery,length of stay were collected.Moreover for each patients were registered data about relapse of appendicitis and hospital admission due to intestinal obstruction.RESULTS From 1997 to 2013 in the Bergamo district we collected 16544 cases of AA,with a crude incidence rate of 89/100000 inhabitants per year; mean age was 24.51 ± 16.17,54.7% were male and the mean Charlson's comorbidity index was 0.32 ± 0.92.Mortality was < 0.0001%.Appendectomy was performed in 94.7% of the patients and the mean length of stay was 5.08 ± 2.88 d; the cumulative hospital stay was 5.19 ± 3.36 d and 1.2% of patients had at least one further hospitalization due intestinal occlusion.Laparoscopic appendectomy was performed in 48% of cases.Percent of 5.34 the patients were treated conservatively with a mean length of stay of 3.98 ± 3.96 d; the relapse rate was 23.1% and the cumulative hospital stay during the study period was 5.46 ± 6.05 d.CONCLUSION The treatment of acute appendicitis in Northern Italy is slowly changing,with the large diffusion of laparoscopic approach; conservative treatment of non-complicated appendicitis is still a neglected option,but rich of promising results.

Peritoneal carcinomatosis

Several gastrointestinal and gynecological malignancies have the potential to disseminate and grow in the peritoneal cavity.The occurrence of peritoneal carcinomatosis(PC)has been shown to significantly decrease overall survival in patients with liver and/or extraperitoneal metastases from gastrointestinal cancer.During the last three decades,the understanding of the biology and pathways of dissemination of tumors with intraperitoneal spread,and the understanding of the protective function of the peritoneal barrier against tumoral seeding,has prompted the concept that PC is a loco-regional disease:in absence of other systemic metastases,multimodal approaches combining aggressive cytoreductive surgery,intraperitoneal hyperthermic chemotherapy and systemic chemotherapy have been proposed and are actually considered promising methods to improve loco-regional control of the disease,and ultimately to increase survival.The aim of this review article is to present the evidence on treatment of PC in different tumors,in order to provide patients with a proper surgical and multidisciplinary treatment focused on optimal control of their locoregional disease.

Esophagogastric junction gastrointestinal stromal tumor:Resection vs enucleation

Esophageal gastrointestinal stromal tumors(GISTs) are extremely uncommon,representing approximately 5% of GISTs with the majority of esophageal GISTs occurring at the esophagogastric junction(EGJ).The treatment options available for these GISTs are fairly controversial.Many different options are nowadays at our disposal.From surgery to the target therapies we have the possibility to treat the majority of GISTs,including those which are defined as unresectable.The EGJ GISTs represent a stimulating challenge for the surgeon.The anatomical location increases the possibility of postoperative complications.As the role of negative margins in GIST surgery is still controversial and the eff icacy of target therapy has been demonstrated,why not treat EGJ GISTs with enucleation and,where indicated,adjuvant target therapy?

Peritoneal seeding from appendiceal carcinoma:A case report and review of the literature

Non-carcinoid appendiceal malignancies are rare entities,representing less than 0.5% of all gastrointestinal malignancies.Because of their rarity and particular biological behavior,a substantial number of patients affected by these neoplasms do not receive appropriate surgical resection.In this report,we describe a rare case of primary signetring cell carcinoma of the appendix with peritoneal seeding which occurred in a 40-year old man admitted at the Emergency Surgery Department with the clinical suspicion of acute appendicitis.After a surgical debulking and right hemicolectomy,the patient had systemic chemotherapy according to FOLFOX protocol.After completion of the latter,the patient underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.This report offers a brief review of the literature and suggests an algorithm for the management of non-carci-noid appendiceal tumors with peritoneal dissemination.

Antimicrobial management of intra-abdominal infections:Literature's guidelines

Antimicrobial management of severe intra-abdominal infections (IAIs) involves a delicate balance of optimizing empirical therapy,which has been shown to improve clinical outcomes,while simultaneously reducing unnecessary antimicrobial use.Two sets of guidelines for the management of intra-abdominal infections were recently published.In 2010,the Surgical Infection Society and the Infectious Diseases Society of America (SIS-IDSA) created guidelines for the diagnosis and management of complicated IAIs.The new SIS-IDSA guidelines replace those previously published in 2002 and 2003.The World Society of Emergency Surgery (WSES) guidelines represent additional contributions,made by specialists worldwide,to the debate regarding proper antimicrobial drug methodology.These guidelines represent the conclusions of the consensus conference held in Bologna,Italy,in July 2010 during the first congress of the WSES.

Laparoscopic management of intra-abdominal infections:Systematic review of the literature

AIM: To investigate the role of laparoscopy in diagnosis and treatment of intra abdominal infections.METHODS: A systematic review of the literature was performed including studies where intra abdominal infections were treated laparoscopically.RESULTS: Early laparoscopic approaches have become the standard surgical technique for treating acute cholecystitis. The laparoscopic appendectomy has been demonstrated to be superior to open surgery in acute appendicitis. In the event of diverticulitis, laparoscopic resections have proven to be safe and effective procedures for experienced laparoscopic surgeons and may be performed without adversely affecting morbidity and mortality rates. However laparoscopic resection has not been accepted by the medical community as the primary treatment of choice. In high-risk patients, laparoscopic approach may be used for exploration or peritoneal lavage and drainage. The successful laparoscopic repair of perforated peptic ulcers for experienced surgeons, is demonstrated to be safe and effective. Regarding small bowel perforations, comparative studies contrasting open and laparoscopic surgeries have not yet been conducted. Successful laparoscopic resections addressing iatrogenic colonic perforation have been reported despite a lack of literature-based evidence supporting such procedures. In post-operative infections, laparoscopic approaches may be useful in preventing diagnostic delay and controllingthe source.CONCLUSION: Laparoscopy has a good diagnostic accuracy and enables to better identify the causative pathology; laparoscopy may be recommended for the treatment of many intra-abdominal infections.

Gastrointestinal stromal tumor and mitosis,pay attention

The difference between stages I and ]]I of gastric gas- trointestinal stromal tumor depends principally on the number of mitosis. According with TNM classification, the presence in the tumor of high mitotic rate deter- mines the upgrading. Many studies exposed different count techniques in evaluating the number of mitosis. An international standardized method to assess mitotic rate is needed.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in epithelial ovarian cancer: State of the art

Advanced stage epithelial ovarian cancer(EOC) is diffi cult to treat with low overall cure rates. A new strategy combining maximal cytoreductive surgery(CRS) with intraoperative hyperthermic intraperitoneal chemotherapy(HIPEC) has been proposed to treat advanced stage EOC in the primary setting. Numerous small, heterogeneous studies have been conducted exploring outcomes in patients with predominantly advanced, recurrent or refractory disease treated with CRS + HIPEC. Although morbidity rates approaching 35% have been reported, oncologic outcomes are promising. Incorporation of HIPEC for the treatment of primary EOC has continued to gain interest. Several prospective phase 2 clinical trials were recently completed evaluating the impact of CRS + HIPEC in the primary setting. This article will briefl y discuss the benefi ts of optimal surgical cytoreduction and the theoretical basis of intraperitoneal chemotherapy in patients with advanced stage EOC, and will then review existing literature describing oncologic outcomes in EOC patients treated with HIPEC in the primary setting.

Preoperative colonic stents vs emergency surgery for acute left-sided malignant colonic obstruction: meta-analysis with systematic review of the literature

AIM To investigate by meta-analytic study and systematic review, advantages of colonic stent placement in comparison with emergency surgery.METHODS We conducted an extensive literature search by PubMed, Google Scholar, Embase and the Cochrane Libraries. We searched for all the papers in English published till February 2016, by applying combinations of the following terms: Obstructive colon cancer, colon cancer in emergency, colorectal stenting, emergency surgery for colorectal cancer, guidelines for obstructive colorectal cancer, stenting vs emergency surgery in the treatment of obstructive colorectal cancer, selfexpanding metallic stents, stenting as bridge to surgery. The study was designed following the PrismaStatement. By our search, we identified 452 studies, and 57 potentially relevant studies in full-text were reviewed by 2 investigators; ultimately, 9 randomized controlled trials were considered for meta-analysis and all the others were considered for systematic review.RESULTS In the meta-analysis, by comparing colonic stenting(CS) as bridge to surgery and emergency surgery, the pooled analysis showed no significant difference between the two techniques in terms of mortality [odds ratio(oR) = 0.91], morbidity(oR = 2.38) or permanent stoma rate(oR = 1.67); primary anastomosis was more frequent in the stent group(oR = 0.45; P = 0.004) and stoma creation was more frequent in the emergency surgery group(oR = 2.36; P = 0.002). No statistical difference was found in disease-free survival and overall survival. The pooled analysis showed a significant difference between the colonic stent and emergency surgery groups(oR = 0.37), with a significantly higher 1-year recurrence rate in the stent group(P = 0.007).CONCLUSION CS improves primary anastomosis rate with significantly high 1-year follow-up recurrence and no statistical difference in terms of disease-free survival and overall survival.

Advanced ovarian cancer: Neoadjuvant chemotherapy plus surgery and HIPEC as up-front treatment

Epithelial ovarian cancer （EOC） is one of the most com-mon malignancies and one of the principal causes of death in gynecological neoplasms. The majority of EOC patients present with an advanced International Fed-eration of Gynecology and Obstetrics stage disease. The current standard treatment for these patients con-sists of complete cytoreduction and combined systemic chemotherapy of a platinum agent and paclitaxel. Even if the majority of patients with EOC respond to frst-line platinum based chemotherapy, almost 20% of them are resistant or refractory. According to these data, the main risk is for a certain number of patients to have undergone cytoreductive surgery （CRS） and subsequent hyperthermic intraoperative peritoneal chemotherapy （HIPEC） in a useful way. Radical surgery, especially in advanced cases, is associated with a high incidence of postoperative morbidity and mortality, which could be increased by the HIPEC. Every effort should be made for previously selected patients to improve outcome and optimize resources. Over the last decade, new options have been introduced to prolong survival. Im-proved long-term results can be achieved using CRS in combination with intraoperative HIPEC. This combina-tion has also been used in an up-front setting. Contro-versial outcomes have been reported for neoadjuvant platinum-based chemotherapy. Different papers have been published reporting discordant results. Further studies are needed.

Value of neoadjuvant chemotherapy in advanced ovarian cancer

Data regarding the role of neoadjuvant chemotherapy(NACT) are not definitive. Several randomized trials and meta-analyses demonstrate that this chemotherapy regimen decreases the morbidity and mortality rates and increases complete cytoreduction rates. If combined with hyperthermic intraperitoneal chemotherapy(HIPEC), NACT could potentially further improve upon these already promising results. Moreover the use of NACT could help in evaluating the chemo-sensitivity of the cancer, thus preventing unnecessary HIPEC procedures in chemo-resistant patients. NACT should definitely be considered as a preferred regimen in the management of advanced ovarian cancer, especially in association with cytoreductive surgery + HIPEC procedure in the context of a multidisciplinary team management in an experienced cancer centre.

Peritoneal carcinomatosis from advanced ovarian cancer: To treat or not to treat ethical issues suggested by a case study

This article provides a brief description of an epithelial ovarian cancer （EOC） case （stage Ⅳ） treated with the association of complete CytoReductive Surgery and hy-pertermic intraPEritoneal chemotherapy （HIPEC）. The use of HIPEC in EOC makes theoretic sense in view of the high rates of recurrence following standard treat-ment, but there are no randomized clinical trial to date and HIPEC for these patients still represents a radical treatment where the choice of no treatment may be acceptable since defnitive cure is unlikely. We reviewed the entire decision making process considering the risk/beneft of the procedure in term of mortality/morbidity, the quality of life and the psychological profile of the patient 1 year after surgery. The platform World Health Organization-International Classification of Function-ing, Disability and Health that permits evaluation of the person in relation to the psycho-social context is pre-sented. A person-centred approach and assessment of health-related quality-of-life and disability in EOC survi-vors are of central importance for decision making.

Acknowledgments to reviewers of World Journal of Obstetrics and Gynecology

Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of World Journal of Obstetrics and Gynecology.The editors and authors of the articles submitted to the journal are grateful to the following reviewers for evaluating the articles(including those published in this issue and those rejected for this issue)during the last editing time period.

The artificial intelligence evidence-based medicine pyramid

Several studies exist in the literature regarding the exploitation of artificial intelligence in intensive care.However,an important gap between clinical research and daily clinical practice still exists that can only be bridged by robust validation studies carried out by multidisciplinary teams.