GLUT 1 receptor expression and circulating levels of fasting glucose in high grade serous ovarian cancer.

In recent years, the poorly remarkable goals achieved in terms of patients' important outcomes for ovarian cancer have fueled our interest toward the study of its metabolic roots. Within this research pipeline, we assessed the association between the expression of the glucose transporter GLUT1, as expressed at the tumor tissue level, and circulating pre-surgical levels of fasting glucose in a case series including data from 40 patients with high FIGO stage serous ovarian cancer. Patients who provided data to the current analysis were randomly selected from a larger cohort. To our purposes, the procedures related to serum and tissue collection, storage and biomarker assessment were highly standardized and centralized at the institutional laboratories. The GLUT1 antibody SPM498 SPRING (REF. E13810) was used at a 1:500 dilution in 2 µm slides. Staining for GLUT1 was observed at the cell membrane level in all the cases assessed, but strong staining was described in 29 (72.5%) of them. The agreement between the two independent reviewers was 100%. Strong GLUT1 staining was inversely associated with circulating levels of fasting glucose, with a particularly striking difference for patients in the lowest fasting glucose tertile (p = 0.044). These results support the biological plausibility of the association of interest. If confirmed in larger studies, our findings may help clarify the potentials of biomarkers related to energy metabolism in terms of prognosis definition, treatment assignment, and outcome interpretation for patients with high FIGO stage serous ovarian cancer.

Cytoreduction (Peritonectomy Procedures) Combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Advanced Ovarian Cancer: Retrospective Italian Multicenter Observational Study of 511 Cases.

PURPOSE: The aim of this study was to help with the process of selecting patients with advanced ovarian cancer to undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) by analyzing outcome data at distinct clinical time points reflecting the natural history of the disease. METHODS: In a retrospective Italian multicenter study investigating patients with advanced ovarian cancer who underwent CRS plus HIPEC between 1998 and 2014, we analyzed data for consecutive patients at eight treatment time points: primary debulking surgery (PDS); interval debulking surgery after partial response, after no response, and after a pathologic complete response to neoadjuvant chemotherapy; first recurrence with a progression-free interval >12, <12 months, or >12 months in patients who underwent further chemotherapy before CRS and HIPEC; and patients who underwent two or more CRS procedures and chemotherapy lines before CRS and HIPEC. RESULTS: The 511 enrolled patients underwent 3373 procedures; 72.6% achieved complete cytoreduction, with an overall major morbidity of 17.4%. At a median follow-up of 53.8 months, overall survival (OS) was 54.2 months (95% confidence interval [CI] 44-58.4) and progression-free (PFS) survival was 16.6 months (95% CI 14.7-19.1). Outcome analysis in patients in whom CRS plus HIPEC was used for primary advanced cancer or recurrent ovarian cancer showed significant differences in OS and PFS according to the time points analyzed. Multivariate analysis identified completeness of CRS, Peritoneal Cancer Index, and the times when patients underwent CRS plus HIPEC as independent prognostic factors. CONCLUSIONS: This selective information on survival should help in interpreting the findings from ongoing randomized studies focusing on CRS plus HIPEC in patients with advanced ovarian cancer.

Mesothelial cyst of the round ligament of the liver.

A 34-year-old man was admitted in our department with a 3 months history of epigastric pain, abdominal distension and tenderness. Helical computed tomography scan and magnetic resonance imaging showed a 10 cm low-density fluid-filled polilobate cystic lesion with internal septations and calcifications located between the left lobe of the liver, shorter gastric curvature, pancreas and mesocolon. Laparoscopic exploration was performed. Macroscopically the lesion was a unilocular serous cyst with a thick fibrous wall. Histopathology revealed a thin fibrous wall with a single layer of flattened to cuboidal mesothelial cell lining lacking any cellular atypia. The patient is currently alive without evidence of recurrence at 6 months. Cysts of mesothelial origin are rare lesions seen more frequently in young and middle-aged women, mostly benign and located in the mesenteries or omentum. Diagnosis is usually based on clinical examination and radiographic imaging. Immunohistochemistry is used to differentiate histologic type, with simple mesothelial cysts being positive for cytokeratins and calretinin and negative for CD31. The laparoscopic approach appears safe, feasible and less-invasive without compromising surgical principles and today should be considered the gold standard in most cases.

Third international conference of the European Union Network of Excellence on gastric and esophagogastric junction cancer, Cologne, Germany, June 2012.

In 2012 the European Union Network of Excellence on gastric and esophagogastric junction cancer (EUNE) held its third conference in Cologne, Germany. The main themes discussed included translational research, standard and audit, early diagnosis, development of surgical treatment, adequate surgery for EGJ cancer, adjuvant and neoadjuvant treatment, prevention of peritoneal carcinomatosis and finally education and training. The meeting was attended by 150 experts from 18 different countries.

GASTRICHIP: D2 resection and hyperthermic intraperitoneal chemotherapy in locally advanced gastric carcinoma: a randomized and multicenter phase III study.

BACKGROUND: In Europe, gastric cancer remains diagnosed at advanced stage (serosal and/or lymph node involvement). Despite curative management combining perioperative systemic chemotherapy and gastrectomy with D1-D2 lymph node dissection, 5-year survival rates of T3 and/or N + patients remain under 30%. More than 50% of recurrences are peritoneal and/or locoregional. The use of adjuvant hyperthermic intraperitoneal chemotherapy that eliminates free cancer cells that can be released into peritoneal cavity during the gastrectomy and prevents peritoneal carcinomatosis recurrences, was extensively evaluated by several randomized trials conducted in Asia. Two meta-analysis reported that adjuvant hyperthermic intraperitoneal chemotherapy significantly reduces the peritoneal recurrences and significantly improves the overall survival. As it was previously done for the evaluation of the extension of lymph node dissection, it seems very important to validate on European or caucasian patients the results observed in trials performed in Asia. METHODS/DESIGN: GASTRICHIP is a prospective, open, randomized multicenter phase III clinical study with two arms that aims to evaluate the effects of hyperthermic intraperitoneal chemotherapy with oxaliplatin on patients with gastric cancer involving the serosa and/or lymph node involvement and/or with positive cytology at peritoneal washing, treated with perioperative systemic chemotherapy and D1-D2 curative gastrectomy. Peroperatively, at the end of curative surgery, patients will be randomized after preoperatively written consent has been given for participation. Primary endpoint will be overall survival from the date of surgery to the date of death or to the end of follow-up (5 years). Secondary endpoint will be 3- and 5-year recurrence-free survival, site of recurrence, morbidity, and quality of life. An ancillary study will compare the incidence of positive peritoneal cytology pre- and post-gastrectomy in two arms of the study, and assess its impact on 5-year survival. The number of patients to be randomized was calculated to be 306. TRIAL REGISTRATION: EudraCT number: 2012-005748-12, ClinicalTrials.gov identifier: NCT01882933.

Imagine a world without cancer.

BACKGROUND: Since the "War on Cancer" was declared in 1971, the United States alone has expended some $300 billion on research, with a heavy focus on the role of genomics in anticancer therapy. Voluminous data have been collected and analyzed. However, in hindsight, any achievements made have not been realized in clinical practice in terms of overall survival or quality of life extended. This might be justified because cancer is not one disease but a conglomeration of multiple diseases, with widespread heterogeneity even within a single tumor type. DISCUSSION: Only a few types of cancer have been described that are associated with one major signaling pathway. This enabled the initial successful deployment of targeted therapy for such cancers. However, soon after this targeted approach was initiated, it was subverted as cancer cells learned and reacted to the initial treatments, oftentimes rendering the treatment less effective or even completely ineffective. During the past 30 plus years, the cancer classification used had, as its primary aim, the facilitation of communication and the exchange of information amongst those caring for cancer patients with the end goal of establishing a standardized approach for the diagnosis and treatment of cancers. This approach should be modified based on the recent research to affect a change from a service-based to an outcome-based approach. The vision of achieving long-term control and/or eradicating or curing cancer is far from being realized, but not impossible. In order to meet the challenges in getting there, any newly proposed anticancer strategy must integrate a personalized treatment outcome approach. This concept is predicated on tumor- and patient-associated variables, combined with an individualized response assessment strategy for therapy modification as suggested by the patient's own results. As combined strategies may be outcome-orientated and integrate tumor-, patient- as well as cancer-preventive variables, this approach is likely to result in an optimized anticancer strategy. SUMMARY: Herein, we introduce such an anticancer strategy for all cancer patients, experts, and organizations: Imagine a World without Cancer.

Gastrointestinal stromal tumors of the stomach: the role of laparoscopic resection. Single-centre experience of 38 cases.

INTRODUCTION: Laparoscopic resection is considered the gold standard of treatment only for small gastric gastrointestinal stromal tumor (GIST). MATERIALS AND METHODS: Between January 2004 and September 2012, 38 consecutive gastric GISTs were operated on by laparoscopic approach, without conversions. Thirty-five cases were primary GISTs and three were bleeding GISTs with hepatic metastases non-responding to conservative therapy treated by emergency surgery. RESULTS: Median tumor size was 3.63 cm (1.8-17 cm). In two cases tumor size was <2 cm, between 2 and 5 cm in 26 cases, between 5 and 10 cm in eight cases, and >10 cm in two cases. In two cases, localization was in the cardia, fundus in ten cases, lesser curve in 11 cases, greater curve in 12 cases, and antrum in three cases. We performed 24 wedge resections, eight transgastric resections and six antrectomies. An Endo-GIA™ was used in 25 cases, and a manual laparoscopic reconstruction with extramucosal suture was performed in 13 cases. No postoperative mortality and morbidity was observed. The routine use of laparoscopy allowed us to perform resections in 100 % of cases, even in those where preoperative imaging suggested an open approach according to the current guidelines. CONCLUSIONS: The use of a pre-resection endobag avoids spillage and seeding, thus increasing the possibility of resection. In conclusion, we consider the laparoscopic approach as mandatory in all cases, always considering the possibility of converting to the open technique when necessary.

Spigelian-cryptorchidism syndrome: Lesson based on a case report.

The Spigelian hernia is a abdominal wall hernia that originates from a discontinuity of the Spigelian fascia located lateral to the rectus abdominis muscle. It can be acquired in adults or congenital in newborns. In very rare cases in male it can be associated with cryptorchidism, in which case it is known as "Spigellian-Cryptorchidism Syndrome". It can be clinically highlighted with abdominal swelling wall along the semilunar line and intestinal obstruction. The diagnosis, as in all pediatric emergencies, must be timely and the method of choice is ultrasound which allows a rapid localization of the hernia breach and herniated structures. The treatment of choice is surgical with herniopexy and repositioning of the testicle into the scrotal sac, or orchipessy in cases of testicular necrosis. We describe ultrasound characteristics of Spigellian-cryptorchidism syndrome presenting with acute intestinal obstruction in a newborn.

Updates on surgical management of advanced gastric cancer: new evidence and trends. Insights from the First International Course on Upper Gastrointestinal Surgery--Varese (Italy), December 2, 2011.

Between the Ninth International Gastric Cancer Congress (IGCC) in South-Korea (Seoul, 2011) and the Tenth IGCC in Italy (Verona, 2013), the Insubria University organized the First International Course on Upper Gastrointestinal Surgery (Varese, December 2, 2011), with the patronage of Italian Research Group for Gastric Cancer (IRGGC) and the International Gastric Cancer Association (IGCA). The Course was intended to be a comprehensive update and review on advanced gastric cancer (GC) staging and treatment from well-known international experts. Clinical, research, and educational aspects of the surgeon's role in the era of stage-adapted therapy were discussed. As highlighted in the meeting, in this final document we summarize and thoroughly analyze (with references only for well-acquired randomized control trials) the new and old open problems in surgical management of advanced GC. Between the Ninth (Seoul, 2011) and the Tenth (Verona,2013) International Gastric Cancer Congress, the First International Course on Upper Gastrointestinal Surgery (Varese, December 2, 2011) was organized by the University of Insubria. This congress received the patronage of the International Gastric Cancer Association and the Italian Research Group for Gastric Cancer. The aim was to discuss open issues in surgical management of advanced gastric malignancies. We considered the opinions of several recognized experts in the field from both the Eastern and Western world, focused on definition problems and oncological and technical issues to define the current principles of advanced gastric cancer (GC) surgery.

Peritoneal carcinomatosis: cytoreductive surgery and HIPEC--overview and basics.

Tumor involvement of the peritoneum-peritoneal carcinomatosis-is a heterogeneous form of cancer that had been generally regarded as a sign of systemic tumor disease and as a terminal condition. The multimodal treatment approach for patients with peritoneal carcinomatosis, which had been conceived and developed, consists of what is known as cytoreductive surgery, followed by hyperthermic intraperitoneal chemotherapy (HIPEC). Depending on the tumor mass as assessed intraoperatively and the histopathological differentiation, patients who undergo cytoreductive surgery and HIPEC have a significant survival benefit. Mean increases in the survival period ranging from six months to up to four years have now been reported. In view of the substantial logistic effort and the extent of the surgery involved, this treatment approach represents a major challenge both for patients and for surgical oncologists, as well as for the members of the overall interdisciplinary structure required, which includes oncology, anesthesiology and intensive care, psycho-oncology, and patient management. The surgical procedures alone may take 8-14 hr. The present paper provides an overview of the basis for the approach and the use of specialized classifications and quantitative prognostic indicators.

Prevention of complications following pelvic exenteration with the use of mammary implants in the pelvic cavity: Technique and results of 28 cases.

BACKGROUND: With the evolution of neo-adjuvant therapy and the introduction of peritonectomy with chemotherapy in surgical practice, pelvic exenteration has taken second place in the treatment of advanced pelvic tumors. This surgery remains the first of choice for the treatment of T4 superior and medium rectal tumors that are not susceptible to neo-adjuvant radiochemotherapy, for uterine tumors and cervical FIGO IV T4, for pelvic recurrence and for T4 bladder tumors. After a pelvic exenteration the pelvic cavity becomes occupied by the intestinal loops, causing an increase in the risk of short and long-term complications such as radiation enteritis in the case of post-operative radiotherapy, occlusions, and enteric fistulas that could be avoided by isolating the small intestine in the pelvic cavity. METHODS: With this aim we positioned a mammary prosthesis (implant) in the cavity of the last 28 cases we treated, and did not observe complications related to the prosthetic implant. RESULTS: No early or delayed complications, such as occlusions or fistulas, were observed. All the patients treated underwent adjuvant radiotherapy with no evidence of radiation enteritis. Ten patients were recanalized with removal of the implant, ultra-low rectal anastomosis was performed in six cases and colo-anal anastomosis was performed in four cases. Eight patients were not recanalized, six distance due to recurrence and two local recurrence. Nine patients are currently in follow-up, disease free between 1 and 12 months. CONCLUSIONS: We retain the encouraging results observed that the use of mammary implants in the pelvic cavity after pelvic exenteration should be part of the cultural patrimony of the surgeon who approaches this type of major radical surgery.

European single-center experience on 356 operated patients for gastric cancer.

AIM: Surgery in association with lymphadenectomy is the treatment of choice for the gastric adenocarcinoma. Aim is to report our experience in the surgical treatment of gastric cancer in a European center. MATERIAL AND METHODS: A prospectively maintained database identified 515 patients. Staging laparoscopy was performed to rule out peritoneal carcinomatosis in suspicious cases. Type of surgery and lymphadenectomy were determined according to the Japanese guidelines and pathological staging according to the TNM classification. Survival was analysed using the Kaplan-Meier method. RESULTS: Staging laparoscopy avoided 150 (29.1%) unnecessary laparotomies. A total of 356 patients underwent surgery with curative intent. Overall postoperative morbidity and mortality rates were 16.8% and 5.9%, respectively. Two hundred-fifty-one patients (70%) were T3-T4. Negative lymph-nodes were observed in 71 patients (19.9%). One-hundred- seventy-nine were at least stage III. At a mean follow-up of 80.6 months, the overall and disease-free survival rates were 54.4% and 50.6%, respectively. The survival stratification based on the type of lymphadenectomy showed an overall survival rate of 43% and 65.5% in case of D1 and D2 lymphadenectomy, respectively. Based on the tumor stage the overall survival rate was 90%, 62.7%, 36.4% and the disease-free survival was 90%, 54.3%, 31.3%, for stage I, II and III, respectively. CONCLUSIONS: Total or subtotal gastrectomy with D2 lymphadenectomy and adjuvant therapy for the treatment of locally advanced gastric cancer proved a valuable strategy. Staging laparoscopy is recommended. KEY WORDS: Gastric cancer, Laparoscopy, Lymphadenectomy, Prognosis, Surgery.

Transanal drainage tube: alternative option to defunctioning stoma in rectal cancer surgery?

BACKGROUND: Anastomotic leakage (AL) remains the most dreaded complication after rectal cancer surgery. The aim of this study was to evaluate the role of transanal drainage tube in reducing the incidence, severity and hospital costs respect to defunctioning stoma (DS). METHODS: Considering 429 patients consecutively operated for rectal adenocarcinoma, the tube was placed in 275 (Group A) and not placed in 154 (Group B) patients. A DS was created in a subgroup of 54 patients among the latter. RESULTS: The incidence of AL was significantly higher in Group B (P=0.007). In patients with DS, the incidence was higher than Group A (P=NS). Grade C complications were significantly higher in Group B (P=0.006) and Grade B complications were significantly higher in patients with DS (P=0.03). Estimated economic benefit was 4,000 Euros for each patient. CONCLUSIONS: Transanal drainage tube may be a safe and effective alternative to DS in many cases. The incidence of leakage and Grade C complications are reduced albeit not significantly but Grade B complications are significantly lower. Although the AL incidence was similar in our experience, the tube allows to avoid a stoma-related consequence and the need for reversal procedure with economic benefit.

Evidence-based medicine in the treatment of peritoneal carcinomatosis: Past, present, and future.

The current treatment of peritoneal surface malignancies (PSMs) is moving from a nihilistic approach, into a combined modality approach offering selected patients long-term survival. As primary PSM are rare, extrapolation of data from clinical trials of related disease is necessary to develop treatment guidelines. Secondary PSM are more common, and therefore, treatment guidelines should be developed based on prospective clinical trials. We reviewed the published and ongoing clinical trials studying the treatment of PSM.

Peritoneal carcinomatosis from ovarian epithelial primary: combined aggressive treatment.

UNLABELLED: Cytoreductive surgery followed by platinum based systemic chemotherapy is an effective treatment for advanced ovarian epithelial carcinoma, resulting in up to 80% complete response (CR) rate; however only 30% of patients reaches 5-year survival. The low extra-abdominal relapse attitude leads to consider the opportunity of treatment intensification combining aggressive cytoreductive surgery with locoregional chemotherapy for FIGO stage III/IV ovarian carcinoma recurrent after the first-line chemotherapy, having still a curative intent. PATIENTS AND METHODS: An "open" intra-abdominal hyperthermic perfusion with 25 mg/m(2)/lt cisplatin of perfusate or 50 mg/m(2)cisplatin plus 15 mg/m(2)doxorubicin was carried out throughout the abdomino-pelvic cavity on 42 patients affected by peritoneal carcinomatosis from ovarian primary, soon after tumor removal en bloc with regional involved peritoneum. Clinical and oncologic data have been prospectively recorded on a dedicated database. RESULTS: Forty-two patients, submitted to peritonectomy, achieved no residual macroscopic disease in 83% of the cases. Hyperthermic chemoperfusion was performed in 95% of the patients. Major complications were observed in 21.4%, being directly correlated to the duration of the surgical procedure (p=0.03). The operative mortality was 4.7%. At a mean follow up of 22 months, the overall 3-year survival was 61.4%, with a median survival of 41 months. CONCLUSION: Complete cytoreduction is possible for the majority of patients, allowing encouraging survival to be reached. Careful selection of patients could reduce surgical risk and further improve survival.

MiR-204 down-regulation elicited perturbation of a gene target signature common to human cholangiocarcinoma and gastric cancer.

BACKGROUND & AIMS: There is high need of novel diagnostic and prognostic tools for tumors of the digestive system, such as gastric cancer and cholangiocarcinoma. We recently found that miR-204 was deeply downregulated in gastric cancer tissues. Here we investigated whether this was common to other tumors of the digestive system and whether this elicited a miR-204-dependent gene target signature, diagnostically and therapeutically relevant. Finally, we assessed the contribution of the identified target genes to the cell cycle progression and clonogenicity of gastric cancer and cholangiocarcinoma cell lines. METHODS: We employed quantitative PCR and Affymetrix profiling for gene expression studies. In silico analysis aided us to identifying a miR-204 target signature in publicly available databases (TGCA). We employed transient transfection experiments, clonogenic assays and cell cycle profiling to evaluate the biological consequences of miR-204 perturbation. RESULTS: We identified a novel miR-204 gene target signature perturbed in gastric cancer and in cholangiocarcinoma specimens. We validated its prognostic relevance and mechanistically addressed its biological relevance in GC and CC cell lines. CONCLUSIONS: We suggest that restoring the physiological levels of miR-204 in some gastrointestinal cancers might be exploited therapeutically.

1st Evidence-based Italian consensus conference on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinosis from ovarian cancer.

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.

Laparoscopic staging of peritoneal surface malignancies.

BACKGROUND: The Peritoneal Cancer Index (PCI) may be used in the intraoperative evaluation of peritoneal surface malignancies to estimate the feasibility of peritonectomy with intraperitoneal hyperthermic chemotherapy perfusion. Although radiologic imaging techniques detect liver and other distant metastases, they do not accurately image small cancer implants on small bowel and its mesentery, thus making a CT-PCI classification impossible. RESULTS: We used videolaparoscopy to stage 97 cases of peritoneal carcinomatosis, and achieved full laparoscopic PCI assessment in 96/97 cases, while only 2/96 cases were understaged. In all our cases where peritonectomy followed diagnostic laparoscopy, we found good correlation between the open surgery data and the laparoscopic PCI. There was no mortality and no neoplastic colonization at the trocar port site. We excluded patients from peritonectomy if the staging laparoscopy showed a massive involvement of their small bowel or mesentery. CONCLUSION: Laparoscopy is a useful tool in peritoneal surface malignancies; it allows direct visualization even of small cancer nodules and provides a reliable assessment of the feasibility of peritonectomy.