Risk Of Peritoneal Recurrence Research Articles

Stenting as bridge to surgery versus upfront emergency resection for non-metastatic left sided obstructing colorectal cancer: risk of peritoneal recurrence and long-term outcomes.

Oncological outcomes of stenting as a bridge to surgery (SBTS) remain a major concern, despite perioperative benefits it offers. This study aims to evaluate the differences in recurrence patterns and survival in patients with non-metastatic, obstructing left sided colon cancers treated by SBTS versus upfront emergency surgery (ES). This is a retrospective, single-centre cohort study of 227 consecutive patients with non-metastatic, obstructing left sided colon cancer between 2007 and 2016. Primary outcomes were pattern of recurrence, and survival. Univariate, bivariate and multivariate logistic regression were done to determine relationships between factors and recurrence. Kaplan Meier curves and log rank tests were used to analyse survival outcomes. Of the 227 patients included, 62 underwent SBTS and 165 underwent upfront ES. There was a higher rate of peritoneal recurrence in SBTS group (27.4 vs 15.2% p = 0.034), with no difference observed in overall, liver or lung recurrences. No significant difference in overall survival (p = 0.11), cancer specific survival (p = 0.35), or recurrence free survival (p = 0.107) was observed. Univariate analysis showed that SBTS (OR 2.12, p = 0.036), diabetes mellitus (DM) (OR 2.58, p = 0.013), T4 (OR 2.81, p = 0.001), N + (OR 4.02, p = 0.001), lymphovascular invasion (OR 2.43, p = 0.011) contributed to a higher rate of peritoneal recurrence. Bivariate analysis showed synergistic relationship between T4 tumors and SBTS: in T4 tumors that underwent SBTS, the odds of having peritoneal recurrence was 6.8 times higher when compared to ES (p = 0.004); whilst in T2/3 tumors there was no significant difference observed (OR 1.33, p = 0.55). Multivariable analysis showed SBTS (OR 2.60, p = 0.04), DM (OR 2.88, p = 0.012), N + (OR 2.97, p = 0.026) were significant predictors for peritoneal recurrence. There are concerns over oncological safety of SBTS even with low rates of stent-related perforation. Higher rates of peritoneal recurrence are seen especially with T4 colon cancers treated with SBTS. SBTS, DM and nodal stage were significant predictors for peritoneal recurrence.

Tumor deposits are associated with a higher risk of peritoneal disease in non-metastatic colorectal cancer patients.

Tumor deposit (TD) is a poor prognostic factor in colorectal cancer (CRC) patients. This study aimed to determine whether TD carry the same risk of peritoneal recurrence as known high-risk (HR) features in CRC patients. A retrospective cohort-study of stage I-III CRC patients from 2010 to 2015 was conducted. TD group was defined by the presence of TD on histopathology whereas HR group was defined by the presence of obstruction, perforation, or T4-stage. A total of 151 patients with CRC were identified, of which 50 had TD and 101 had a HR feature. The overall risk of peritoneal recurrence was higher in the TD group versus HR group (36.0% vs. 19.8%, p = 0.03). The risk of peritoneum as the site of first recurrence was also higher in the TD group (22.0% vs. 12.9%, p = 0.03). Overall cancer recurrence at any site was also higher in the TD group (56.0% vs. 34.7%, p = 0.01). Median time to first recurrence was 1.2 (0.7-1.9) years in the TD group compared to 1.4 (0.8-2.1) years in the HR group (p = 0.31). In non-metastatic CRC patients, TD might have a higher risk of tumor recurrence versus their HRcounterparts. Alternative strategies for surveillance and treatment should be considered.

Combined Prophylactic Hyperthermic Intraperitoneal Chemotherapy and Intraoperative Radiotherapy for Localized Gastroesophageal Junction and Gastric Cancer: A Comparative Nonrandomized Study.

The peritoneum frequently is the only recurrence site after radical resection of gastric cancer. Data suggest that hyperthermic intraperitoneal chemotherapy (HIPEC) and intraoperative radiotherapy (IORT) reduce peritoneal recurrence and possibly improve survival for patients with resected gastric and serosal involvement. This study aimed to evaluate the efficacy of combining prophylactic HIPEC and IORT after radical resection of localized gastric cancer. In this retrospective study, the medical records of adult patients with histologically proven gastric/gastroesophageal adenocarcinoma who underwent radical resection with curative intent were evaluated for recurrence and survival according to whether they received prophylactic HIPEC and IORT. The eligibility criteria were met by 58 patients, 33 of whom underwent prophylactic HIPEC and IORT after radical surgery. Overall, 91% the HIPEC/IORT group and 72% of the surgery-only group had ≤pT3 disease. The median follow-up period was 26.6 months for the HIPEC/IORT group and 50.6 months for the surgery group. Locoregional recurrence occurred for six patients (18.1%) in the HIPEC/IORT group and five patients (20%) in the surgery-only group, with peritoneal metastasis (PM) occurring in respectively three (9%) and six (24%) patients. The median recurrence-free survival (RFS) duration was 23.2 months (95% confidence interval [CI] 6.5-39.9 months) for the HIPEC/IORT group versus 24.8 months (95% CI 0.0-51.1 months) for the surgery-only group (p = 0.88), and the corresponding 5-year overall survival (OS) estimates were 69% and 58%. Prophylactic HIPEC and IORT after radical surgery for localized gastric or gastroesophageal cancer did not improve RFS or OS for an unselected group of patients at risk for peritoneal recurrence.

A genomically stable molecular type of gastric cancer as a predictor of peritoneal relapse after radical surgical treatment

Peritoneal metastases are commonly associated with gastric cancer (GC) recurrence after radical treatment. Thus, patients at a high risk of peritoneal relapse require adjuvant intraperitoneal chemotherapy during the initial treatment. Along with clinical and morphological predictors of peritoneal relapse, another approach in surgical oncology is proving to be promising today. It refers to the prediction of the risk of developing metachronous peritoneal metastases in various molecular types of GC.
 Objective — to study the risk of peritoneal relapse in patients with the genomically stable type of GC in comparison to its other molecular types.
 Materials and methods. 37 patients with GC were enrolled into the study and evaluated after the radical treatment. 19 (51.4 %) patients formed a subgroup with peritoneal relapse and 18 patients (48.6 %) were included into a subgroup without metachronous carcinomatosis in the long term. All patients underwent immunohistochemical study for the E‑cadherin (CDH1 gene) expression in a gastric tumor. The genomically stable molecular type was identified on the basis of the aberrant E‑cadherin (CDH1‑mutated) tumor phenotype detection.
 Results. There was a statistically significant difference (p = 0.022, χ2 = 5.22) in the degree of aberrant E‑cadherin expression in subgroups of patients with and without peritoneal relapse — 68.4 and 33.3 %, respectively. Hence, it was noted that the genomically stable molecular type had a significant influence on the risk of peritoneal recurrence: the 2‑year peritoneal relapse‑free survival of GC patients with E‑cadherin of aberrant type was 31.6 %, and in GC patients with wild‑type E‑cadherin expression — 71.4 % (p = 0.022). The 2‑year overall survival of GC patients with aberrant type E‑cadherin expression was 36.8 %, whereas in GC patients with E‑cadherin of the wild type — 77.8 % (p = 0.003).
 Conclusions. The study found that the genomically stable molecular type of GC may serve as a predictive factor associated with an increased probability of peritoneal relapse, as well as a prognostic factor due to its negative impact on patient prognosis. The genomically stable molecular type of GC may be used as a tool for forming a cohort of patients with indications for adjuvant intraperitoneal therapy.

Risk of peritoneal recurrence after laparoscopic versus open surgery for pT4 colon cancer. A propensity score-matched analysis from an international cohort.

Background: Peritoneal carcinomatosis (PC) is an uncommon site of recurrence for colon cancer (CC), but it strongly affects prognosis with poor survival after diagnosis. Since no standard treatment has been established yet, efforts should be addressed towards the prevention of its occurrence. In particular, some literature suggested a detrimental effect of laparoscopic surgery in case of pT4 CC. This study aimed to determine the impact of laparoscopy on the development of PC after potentially curative resection for pT4 CC.

Risk Assessment and Preventive Treatment for Peritoneal Recurrence Following Radical Resection for Gastric Cancer.

As the most common recurrence pattern after radical gastric cancer resection, peritoneal recurrence is a major cause of mortality, which affects the prognosis of patients to a very large extent. Peritoneal status and risk of peritoneal recurrence can be evaluated by peritoneal lavage cytology, photodynamic diagnosis, imaging examination, and pathologic analysis. Presently, there is no standard approach for preventing peritoneal recurrence after radical surgery; furthermore, controversies exist regarding the effects of some preventive methods. Among the preventive methods, there are high expectations about the potential of preoperative therapy, surgical skill improvement, hyperthermic intraperitoneal chemotherapy, and postoperative treatment to reduce the incidence of peritoneal recurrence after radical gastrectomy. This study aimed to analyze the results of previous studies on the risk assessment and preventive methods of peritoneal recurrence after radical gastrectomy in recent years. We hope to provide references for better approach to clinical diagnosis and treatment strategies for peritoneal recurrence after radical gastrectomy.

Long-term oncological outcomes and recurrence patterns in early-stage cervical cancer treated with minimally invasive versus abdominal radical hysterectomy: The Norwegian Radium Hospital experience

ObjectiveTo compare long-term oncological outcomes in early-stage cervical cancer (CC) patients treated with minimally invasive radical hysterectomy (MIRH) versus abdominal radical hysterectomy (ARH), with a focus on recurrence patterns, tumor sizes, and conization. MethodsThis single-institution, retrospective study consisted of stage IA1-IB1 (FIGO 2009) squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma of the cervix, who underwent radical hysterectomy between 2000 and 2017. ResultsOf the 582 patients included, 353 (60.7%) underwent ARH, and 229 (39.3%) MIRH. The median follow-up was 14.4 years in the ARH group and 6.1 years in the MIRH group (p < 0.0001). Among the 96 stage IA patients, only 3 (3.1%) experienced recurrence. Among stage IB1 patients, the risk of recurrence, after adjusting for standard prognostic variables, was twofold higher in the MIRH group versus the ARH group (HR 2.73, 95% CI: 1.56–4.80), and the relative difference was similar in terms of risk of cancer-specific survival (CSS) (HR 3.04, 95% CI: 1.28–7.20) and overall survival (OS) (HR 2.35, 95% CI: 1.21–4.59). In stage IB1 ≤ 2 cm patients without conization MIRH was associated with reduced time to recurrence (TTR) (HR 4.00, 95% CI: 1.67–9.57), CSS (HR 3.71, 95% CI: 1.19–11.58) and OS (HR 3.02, 95% CI: 1.24–7.34). Intraperitoneal combined recurrences accounted for 12 of 30 (40.0%) recurrences in the MIRH group but were not identified after ARH (p = 0.0001). ConclusionsMIRH was associated with reduced TTR, CSS and OS versus ARH in stage IB1 CC patients. The risk of peritoneal recurrence was high, even for tumors ≤2 cm without conization.

Different prognostic significance of signet ring cell histology for early and advanced gastric cancer patients: a systematic review and meta-analysis

ABSTRACT Objective To review relevant studies and perform a meta-analysis to evaluate the prognostic significance of signet ring cell (SRC) histology for gastric cancer (GC) patients. Methods Systematic literature search was performed using PubMed and Embase databases. The relevant data were extracted and the association between SRC histology and survival outcome were evaluated using a fixed-effect or random-effect model. Results A total of 21 studies were included in this meta-analysis. The prevalence of SRC histology varied from 8.7% to 50%. SRC histology type was associated with poorer OS (HR: 1.12, 95%CI: 1.01–1.23, P = 0.034; I2 = 85.1%) and DFS (HR: 1.17, 95%CI: 1.00–1.37, P = 0.040; I2 = 63.6%). The subgroup analysis indicated that SRC type had a better OS than non-SRC type for early GC patients (HR: 0.60, 95%CI: 0.48–0.75, P < 0.001; I2 = 33.7%). However, it was a poor prognostic factor for advanced GC when excluding stage IV patients (HR: 1.18, 95%CI: 1.07–1.29, P < 0.001; I2 = 6.5%). SRC type had a higher risk of peritoneal recurrence than non-SRC type (OR: 1.36, 95%CI: 1.06–1.75, P = 0.017; I2 = 1.3%). Conclusion SRC type had a distinctly different prognostic significance for early and advanced GC patients. SRC type was associated with better survival outcomes in early GC patients, but it was a predictive factor for poor survival in advanced GC patients.

Study protocol of a multicenter phase III randomized controlled trial investigating the efficiency of the combination of neoadjuvant chemotherapy (NAC) and neoadjuvant laparoscopic intraperitoneal hyperthermic chemotherapy (NLHIPEC) followed by R0 gastrectomy with intraoperative HIPEC for advanced gastric cancer (AGC): dragon II trial

BackgroundEven though treatment modalities such as adjuvant systemic radio-chemotherapy and neoadjuvant chemotherapy (NAC) have individually have improved overall survival (OS) and progression-free survival (PFS) rates in advanced Gastric Cancer (AGC), the peritoneum still presides as a common site of treatment failure and disease recurrence. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) has been acknowledged as prophylaxis for peritoneal carcinomatosis (PC) in AGC patients and in this study, we aim at investigating the safety and efficacy of the combination of neoadjuvant laparoscopic HIPEC (NLHIPEC) with NAC in the neoadjuvant phase followed by surgery of curative intent with intraoperative HIPEC followed by adjuvant chemotherapy (AC).MethodsIn this multicenter Phase III randomized controlled trial, 326 patients will be randomly separated into 2 groups into a 1:1 ratio after laparoscopic exploration. The experiment arm will receive the proposed comprehensive Dragon II regimen while the control group will undergo standard R0 D2 followed by 8 cycles of AC with oxaliplatin with S-1 (SOX) regimen. The Dragon II regimen comprises of 1 cycle of NLHIPEC for 60mins at 43 ± 0.5 °C with 80 mg/m2 of Paclitaxel followed by 3 cycles of NAC with SOX regimen and after assessment, standard R0 D2 gastrectomy with intraoperative HIPEC followed by 5 cycles of SOX regimen chemotherapy. The end-points for the study are 5 year PFS, 5 year OS, peritoneal metastasis rate (PMR) and morbidity rate.DiscussionThis study is one of the first to combine NLHIPEC with NAC in the preoperative phase which is speculated to provide local management of occult peritoneal carcinomatosis or peritoneal free cancer cells while NAC will promote tumor downsizing and down-staging. The addition of the intraoperative HIPEC is speculated to manage dissemination due to surgical trauma. Where the roles of intraoperative HIPEC and NAC have individually been investigated, this study provides innovative insight on a more comprehensive approach to management of AGC at high risk of peritoneal recurrence. It is expected that the combination of NLHIPEC with NAC and HIPEC will increase PFS by 15% and decrease PMR after gastrectomy of curative intent.Trial registrationWorld Health Organization Clinical Trials - International Registry Platform (WHO-ICTRP) with Registration ID ChiCTR1900024552, Registered Prospectively on the 16th July, 2019.

Review of the Outcomes of Ovarian Cancer Treated with Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy

Ovarian, fallopian tube and primary peritoneal carcinomas (OVCA) most commonly present in advanced stages and despite aggressive surgical resection and chemotherapy will likely recur. Although OVCA can recur in the liver, chest or brain, it most commonly recurs within the peritoneal cavity. Peritoneal spread is problematic and often results in bowel obstruction and the inability to maintain nutritional goals. Given the lethality of peritoneal disease as well as the difficulty in treating this recurrence pattern, novel tactics to treat peritoneal dissemination have been a focus of research in OVCA. Heated intraperitoneal chemotherapy (HIPEC) has been well studied and is utilized to treat appendiceal malignancies, which similarly involve the peritoneum. HIPEC has been shown to improve survival and decrease the risk of peritoneal recurrence in patients with appendiceal malignancies. This technique has also been shown to improve outcomes in patients with peritoneal metastases due to colorectal cancers and gastric cancers. Over the past three decades, HIPEC has been used to treat OVCA with mixed results. The aim of this paper is to review the use of HIPEC in the treatment of OVCA in the upfront and recurrent setting.

Recurrence pattern and outcomes in T4 colon cancer: A single institution analysis.

706 Background: Patients with T4 colon adenocarcinoma have an increased risk of peritoneal recurrence due to direct seeding malignant cells. It has been theorized that adjuvant chemotherapy may not sterilize the peritoneal surface due to inadequate intraperitoneal concentration. We seek to further define the metastatic pattern, predictors of recurrence, and efficacy of adjuvant treatment in T4 colon cancer. Methods: We reviewed records of 181 adults [median age 71 (22-97)] with T4 N0-3 colon adenocarcinoma at Beaumont Hospital, Michigan from May 2005 –Nov 2015. Baseline factors and data on follow up, metastasis, and survival were collected and analyzed. Results: Overall recurrence rates for N0, N1, and N2 were 27/85 (32%), 17/50 (34%), and 29/46 (63%) (p = 0.001). Locoregional recurrence (LR) rates for N0, N1, and N2 were 21/85 (24.7%), 14/50 (28%), and 21/46 (45.7%) (p = 0.014). Multivariate analysis for distant recurrence was significant only for positive nodes with hazard ratio (HR) 3.3, 95% confidence interval (CI) 1.1-9.9. Multivariate analysis for increased risk of LR was significant for the following variables: perforation (HR 2.7, 95% CI 1.2 – 6.2), lymphovascular invasion (HR 2.7, 95% CI 1.1 – 6.7), positive nodes (HR 2.8, 95% CI 1.2 – 6.9), and positive margins (HR 5.0, 95% CI 2.1 – 12.1). Adjuvant chemotherapy did not decrease risk of LR (HR 0.6, 95% CI 0.3-1.2) or distant recurrence (HR 0.9, 95% CI 0.3-2.8). Multivariate analysis for overall survival revealed the following to be associated with increased risk of mortality: signet ring (HR 2.5, 95% CI 1.2-5.8), positive nodes (HR 2.3, 95% CI 1.2-4.4), positive margin (HR 2.8, 95% CI 1.4-5.8). Adjuvant chemotherapy was not associated with improved survival (HR 0.8, 95% CI 0.4-1.7). Recurrence was strongly associated with colon cancer-specific death with a p &lt; 0.001. Conclusions: Adjuvant chemotherapy is standard of care for most T4 colon cancer patients, however, this data suggests there is no improvement in survival or other significant outcomes. We have identified several risk factors which predict increased risk of LR. This data suggests LR is frequent and not affected by systemic chemotherapy. Prospective trials are needed to reduce the substantial risk of LR in T4 colon cancer.

Preoperative EUS-guided FNA: effects on peritoneal recurrence and survival in patients with pancreatic cancer

EUS-guided FNA (EUS-FNA) is an accurate and relatively safe tissue confirmation method for pancreatic cancer. However, there is concern that this procedure may spread tumor cells along the needle track or within the peritoneum. We aimed to estimate the effect of preoperative EUS-FNA on the risk of peritoneal recurrence and long-term outcomes in resected pancreatic cancer. We retrospectively reviewed records of patients diagnosed with pancreatic cancer who had undergone curative resection between 2009 and 2013 to investigate the overall survival, cancer-free survival, and peritoneal recurrence. Peritoneal recurrence was diagnosed based on image findings or cytology-confirmed ascites. Of 411 patients, 90 underwent preoperative EUS-FNA (EUS-FNA group), whereas 321 did not (non-EUS-FNA group). The median length of follow-up was 16.2 months (range, 2-46). Peritoneal recurrence occurred in 131 patients: 30% (27/90) in the EUS-FNA group versus 32% (104/321) in the non-EUS-FNA group (P= .66). Cancer-free survival or overall survival was not significantly different between the 2 groups: median overall survival of 25.3months in the EUS-FNA group versus 23.7 months in the non-EUS-FNA group (P= .36) and median cancer-free survival of 12.7 months in the EUS-FNA group versus 11.6 months in the non-EUS-FNA group (P= .38). Preoperative EUS-FNA for pancreatic cancer was not associated with an increased rate of peritoneal recurrence or mortality. Therefore, EUS-FNA is an accurate and safe method to obtain suspicious pancreatic mass tissue.

Laparoscopic gastrectomy and adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) using a closed system with turbulent-flow circuit: technical aspects and preliminary results of a pilot study

Intraoperative hyperthermic chemotherapy (HIPEC) is increasingly used in combination with cytoreductive surgery for the treatment of peritoneal carcinomatosis. The potential survival benefit of adjuvant HIPEC after curative gastrectomy has not been conclusively demonstrated. We describe a newly developed closed system for HIPEC and report the preliminary results of a pilot study. Patients with locally advanced gastric carcinoma at a high risk for peritoneal recurrence were identified from a prospectively collected database. Laparoscopic total or subtotal gastrectomy combined with standard D2 lymphadenectomy was performed. Immediately after resection and 15 min before HIPEC treatment, intravenous induction chemotherapy with folinic acid and 5‑fluorouracil was administered. A closed-system HIPEC with turbulent-flow circuit (Combat PRS™, Peritoneum Recirculation System, Galmaz Biotech, Madrid, Spain) was used to perfuse the peritoneal cavity with a solution of oxaliplatin and glucose during 60 min. After washout of the peritoneal cavity and re-establishment of pneumoperitoneum, a Roux-en-Y esophagojejunostomy or gastrojejunostomy was performed. Between June 2017 and February 2018, 6 patients were treated according to this protocol. No major postoperative complications occurred. There were no intra- or postoperative complications related to the HIPEC procedure. All patients are alive and disease-free at 3–11 months of follow-up. The preliminary results of this pilot study indicate the safety and feasibility of the closed HIPEC system with CO2 recirculation in selected patients undergoing laparoscopic total or subtotal gastrectomy for locally advanced gastric carcinoma.

Surgical treatment of peritoneal metastases of colorectal cancer

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may significantly improve overall survival in selected patients with peritoneal metastases of colorectal cancer. For good oncological results complete macroscopic cytoreduction is crucial; furthermore, alinear correlation between peritoneal tumor load, as determined by the peritoneal cancer index (PCI) and overall survival has been demonstrated; therefore, surgical treatment should be initiated as early as possible. Synchronous resection of up to three liver metastases may be performed safely and with good results and no influence on the morbidity. With respect to intraperitoneal chemotherapy, mitomycinC and oxaliplatin are most commonly used and may be regarded as equal; however, for perioperative chemotherapy study results are so far inconclusive with some trials hinting at decreased overall survival following neoadjuvant chemotherapy. Adjuvant therapy is likely to improve overall survival if at least 6cycles are applied. Early detection of peritoneal metastases is difficult at present but might be facilitated in the future by the use of liquid biopsies, which may detect circulating free tumor-specific DNA or RNA. In the meantime, planned second-look laparotomy should be considered for patients at high risk of peritoneal recurrence. In addition, several international studies are currently evaluating the concept of adjuvant or prophylactic HIPEC. The CRS and HIPEC may be repeated in cases of recurrence and should be considered in suitable patients, applying the same criteria as for primary CRS and HIPEC. Arecurrence-free interval of >2years is associated with asignificantly better prognosis.

Locally advanced colorectal cancer: Is a second look surgery and prophylactic HIPEC warranted?

e15056 Background: Peritoneal recurrence/carcinomatosis (PC) after curative surgery for colorectal cancer is the second most common site of recurrence and carries a poor prognosis. PC present relatively in the later stage, are difficult to detect by conventional imaging on follow up, and have limited options to treat after diagnosis. Second look surgery is the only definite option to diagnose early PC and presents an opportunity for disease control by cytoreductive surgery (CRS) and HIPEC. Multiple studies have attempted to identify clinico-pathological risk factors that predict high chances of PC. Our aim is to analyze the recurrence patterns and survival in locally advanced colorectal cancer, in an attempt to identify high risk factors for PC, which can be used as an indication for second look surgery and prophylactic HIPEC in such cases. Methods: Retrospective analysis of a prospectively maintained data of all colorectal cancer patients presenting to a tertiary cancer care referral center in India, from May 2010 to October 2015 was done. All patients who underwent surgery with curative intent and were clinico-pathological stage T4 and/or N2 M0 were included in the analysis. Results: 182 patients underwent curative resection with a clinico-pathological staging of T4 and/or N2 M0. There were 71 recurrences, out of which 30 (42.2%) were peritoneal, 7 (9.9%) were hepatic only while 34 (47.9 %) were non-hepatic systemic or multiple site. For a median follow up of 26 months, the estimated 3 year OS was 78 % while the 3 year DFS was 50.4 %. The median time to diagnosis of peritoneal recurrence was 13 months (4.7 – 55.7). The 3-year OS for patients with peritoneal recurrence was 48.6 % as against 57 % for liver only recurrence and 59.9 % for non liver systemic and multiple site recurrence, with a trend towards poorer survival for peritoneal recurrences, although non-significant (p – 0.377). Conclusions: Locally advanced colorectal cancer has a high risk of peritoneal recurrence which negatively impacts the survival. Well-designed RCTs need to be conducted to identify the high risk factors for PC and whether second look surgery and prophylactic HIPEC in such patients will improve survival with acceptable morbidity and mortality.

Long-term results after proactive management for locoregional control in patients with colonic cancer at high risk of peritoneal metastases.

A major problem in treating patients with peritoneal spread from colorectal cancer is that at diagnosis wide peritoneal involvement often precludes all curative attempts. A possible solution is to identify those patients at risk for peritoneal metastases and intervene early to prevent locoregional disease spread before it develops and, thus, to improve outcome. We analyzed long-term results from a previous study and compared outcomes in 25 patients with advanced colon cancer considered at high risk for peritoneal spread (pT3/pT4 and mucinous or signet ring cell histology) prospectively included and managed with a proactive surgical approach including target organ resection for peritoneal spread plus hyperthermic intraperitoneal chemotherapy (HIPEC) and in 50 retrospectively well-matched controls who underwent standard surgical resection during the same period and in the same hospital by different surgical teams. At 48 months after the study closed, peritoneal metastases and local recurrence developed significantly less often in proactively managed patients than in controls (4 vs 28%) (p < 0.03). Patients in the proactive group also survived longer than control patients (median overall survival 59.5 vs 52 months). Despite similar morbidity, Kaplan-Meier survival curves disclosed significantly longer disease-free and overall survival in the proactive than in the control group (p < 0.05 and <0.04). In patients with advanced colon cancer at risk for peritoneal recurrence, the proactive surgical approach plus HIPEC seems to achieve good locoregional control preventing peritoneal spread thus improving outcome without increasing morbidity. These advantages merit investigation in a multicentric randomized trial.

Monitoring and assessing the intraabdominal therapeutic response for gastric cancer: is second-look laparoscopy the solution?

Exciting translational research is underway to develop predictors of response to therapy and early detection of intraabdominal recurrence after multimodal treatment of advanced solid cancers. Despite efforts and high costs, however, no accurate prognostic or predictive markers have been established for clinical use. Considering the high developmental complexity of molecular cancer predictors, the idea of second-look laparoscopy is too simple. Nevertheless, it may have a central clinical value. Could second-look laparoscopy, as it is proposed by Inoue et al. [1], be used in applied sciences as a diagnostic tool to control, assess, and possibly change adjuvant or palliative systemic treatment after gastrectomy for gastric cancer? A robust and early assessment of treatment response is, particularly in this era, crucial due to very high costs and long-term duration of combined systemic modern chemotherapy regimen and targeted therapy. Evidence of disease progression during this multimodal expensive therapy can lead to a rational decision for cessation of treatment. Indeed, based on the results of an appropriate phase 3 randomized controlled trial [2], the addition of trastuzumab to chemotherapy for patients with human epidermal growth factor receptor type 2 (HER2) advanced, recurrent, or metastatic gastric cancer is suggested [3]. However, despite the significant improvement in response, namely, progression-free survival, the overall survival benefit by the addition of trastuzumab was 12%. Therefore, despite tailoring of trastuzumab treatment specifically to HER2-positive patients, a substantial proportion of these patients do not benefit. We need an ontime assessment to monitor these patients and stop this expensive therapy if peritoneal recurrence or disease progression occurs. To evaluate this diagnostic and therapeutic response approach, Inoue et al. [1] performed a study on secondlook laparoscopy for gastric cancer. Why may this report, published in the October issue of Surgical Endoscopy, have important implications? Peritoneal dissemination is the greatest challenge in the management of gastric cancer for the following reasons. First, peritoneal recurrence is the main cause of treatment failure and death from cancer among patients with an advanced, potentially curable stage of the disease who undergo laparoscopic gastrectomy with D2 node dissection and adjuvant treatment [4–11]. Second, a considerable proportion of these patients already have peritoneal metastases or positive peritoneal cytology results without visible metastatic disease at initial surgery. Third, besides peritoneal cytology, which at the initial stage of peritoneal dissemination requires open or laparoscopic surgery [12, 13], no other robust predictor of the disease exists. Indeed, even the modern imaging positron emission tomography (PET) has limitations for accurate diagnostic staging. Fourth, despite the advent of this exciting cancer genome era [14], it seems that long-term efforts will be required to develop robust genomic predictors of an individual patient risk for peritoneal recurrence and response to a therapy. Therefore, the results of this Japanese study merit our consideration. Inoue et al. [1] report on a second-look laparoscopy for 21 patients who had no clinical evidence of O. Zoras Department of General Surgery, University Hospital of Heraklion, Medical School, University of Crete, Heraklion, Crete, Greece

Application of molecular diagnosis for detection of peritoneal micrometastasis and evaluation of preoperative chemotherapy in advanced gastric carcinoma.

In advanced gastric cancer, peritoneal recurrence is the main cause of death after curative surgical resection. The aim of this report was to describe a novel approach for quantitative genetic diagnosis using peritoneal lavage for the identification of patients at high risk for peritoneal recurrence and for evaluation of the clinical response to intraperitoneal chemotherapy in advanced gastric cancer. Nineteen patients with advanced gastric cancer who underwent staging laparoscopy and intraperitoneal chemotherapy before surgical resection or systemic chemotherapy between June 1999 and September 2001 were enrolled in this study. All peritoneal lavage specimens, collected at both staging laparoscopy and gastrectomy, were subjected to real-time quantitative genetic diagnosis. The reverse transcriptase polymerase chain reaction (RT-PCR) values decreased in 8 cases, stabilized as negative in 5, and increased in 6 during therapy. Patients whose RT-PCR values diminished and were ultimately negative survived except for one, and all but one patient whose values increased during treatment died of recurrence. Quantitative evaluation of genetic changes can provide accurate, useful information on the effects of preoperative intra-abdominal chemotherapy and overall prognosis for patients with advanced gastric cancer.

Different patterns of recurrence in gastric cancer depending on Lauren's histological type: longitudinal study.

The aim of this multicenter longitudinal study was to evaluate the pattern of recurrence in patients submitted to potentially curative surgery for intestinal-type and diffuse-type gastric cancer. The study included 412 patients surgically treated at three Italian surgical departments, subdivided into 273 intestinal-type cases (group A) and 139 diffuse-type cases (group B). Recurrence of disease was found in 41% of group A cases and 65% of group B cases (p < 0.0001). The incidence of locoregional, hematogenous, and peritoneal recurrence was 20%, 19%, and 9% in group A, and 27%, 16%, and 34% in group B, respectively; the difference between the two groups was statistically significant for peritoneal recurrence (p < 0.0001). Multivariate analysis identified as prognostic variables lymph node status, depth of invasion, extent of lymphadenectomy, advanced age, and male gender in group A; depth of invasion, extent of lymphadenectomy, tumor size, and lymph node status, in group B. Whereas in group A the incidence of peritoneal recurrence was limited in all subgroups examined, in group B very high rates were observed in cases with infiltration of the serosa, involvement of second-level lymph nodes, or large tumor size. The notable difference in the risk of peritoneal recurrence between the intestinal and diffuse types should be taken into consideration in the therapeutic approach to gastric cancer.