Positive Peritoneal Lavage Cytology Research Articles

Comparison of prognostic impact between positive intraoperative peritoneal and lavage cytologies in colorectal cancer.

The prognostic value of positive intraoperative peritoneal cytology and lavage cytology, including the differences in their prognostic impact, in colorectal cancer is controversial. We aimed to investigate the prognostic values of positive peritoneal cytology and lavage cytology findings for colorectal cancer and compare their prognostic impact. We retrospectively evaluated 592 clinical stage II-IV colorectal cancer patients who underwent peritoneal cytology (n = 225) or lavage cytology (n = 367) between November 1993 and December 2018. The prognostic factors for cancer-specific survival were identified, and the differences in cancer-specific survival were examined between the patients. The cytology-positive rate was 10.8% (64/592), 17.8% (40/225), and 6.5% (24/367) in the overall, peritoneal cytology, and lavage cytology groups, respectively. Both positive peritoneal cytology (hazard ratio: 2.196) and lavage cytology (hazard ratio: 2.319) were independent prognostic factors. The peritoneal cytology-positive group showed significantly poorer cancer-specific survival than the cytology-negative group (5-year: 3.5% vs. 59.5%; 10-year: 3.5% vs. 46.1%, p < 0.001). Similar results were obtained for lavage cytology (5-year: 14.1% vs. 73.9%; 10-year: 4.7% vs. 63.5%, p < 0.001). The cancer-specific survival was not significantly different between the peritoneal cytology-positive and lavage cytology-positive groups (p = 0.058). Both positive peritoneal and lavage cytology were associated with poorer cancer-specific survival across all colorectal cancer stages. Positive peritoneal and lavage cytology are associated with worse cancer-specific survival in colorectal cancer. The prognostic impact was comparable between positive lavage and peritoneal cytology. Thus, cytology should be a standard assessment modality for colorectal cancer.

Progress and controversy in treatment of gastric cancer patients with positive peritoneal lavage cytology

Progress and controversy in treatment of gastric cancer patients with positive peritoneal lavage cytology

Evaluation of Peritoneal Lavage for Gastric Cancer Staging in Patients Without Ascites Based on Cytology and Carcinoembryonic Antigen

Background: Imaging, cytological examination of ascites (if present), laparosco- py, and peritoneal lavage are performed before surgery for gastric cancer staging. Peritoneal lavage aims to diagnose the microscopic presence of tumor cells on the peritoneal surface. Positive cytology may have a prognostic value that classifies the disorder as stage IV, in which the patient is no longer an elective surgical candidate. Thus, our study was designed to assess the ability of peritoneal lavage to stage gastric cancer in non-ascitic patients based on cytological evaluation and carcinoembryonic antigen (CEA) level measurement. Methods: In our prospective study, we examined gastric cancer patients who were candidates for elective surgery. Upon entering the abdominal cavity and before tu- mor manipulation, normal saline (500 ml) was applied, and the abdominal cavity was thoroughly dispersed. After three minutes, the fluid was drained and addressed to cytological analysis and CEA measurement by radioimmunoassay (RIA). Study var- iables including age, sex, family history, tumor position, pathology, staging, grading, the original tumor size, regional lymph node involvement, and distant metastases were recorded during the pre- and postoperative staging. The association between positive peritoneal lavage cytology and various patients’ characteristics was investigated. Results: In this study, 94 patients were screened. Due to lymphoma and gastrointes- tinal stromal tumor (GIST), two patients were excluded. We examined 92 patients, including 63 males (68.5 %) and 29 females (31.5 %). The mean age of patients was 58.52 ± 11.87 years. The most common tumor location was the esophagogastric junction. Moderately differentiated adenocarcinoma was the most frequent micro- scopic diagnosis. T3 was the most prevalent primary tumor size in 51 patients. Sev- enty-two patients (78.26%) were operable, of whom 18 (19.6 %) were positive for peritoneal lavage cytology. Positive cytology of peritoneal lavage was significantly related to tumor size, tumor grade, serosa/adjacent organ invasion (T4), laparoscopic staging findings, locally advanced disease (R0), and stage of the disease (P &lt; 0.05). In the peritoneal lavage fluid, elevated CEA titers were significantly related to the high-grade tumor (P = 0.012). Conclusion: Our study demonstrated that positive cytology and high CEA titers in peritoneal lavage fluid of gastric cancer patients without ascites are significantly correlated to the advanced stages.

Prognostic factors for cytology-positive gastric cancer: a multicenter retrospective analysis.

The prognosis of patients with gastric cancer and positive peritoneal lavage cytology is poor, even after gastrectomy. Though the standard therapy for this population is radical gastrectomy followed by S-1 chemotherapy, treatments vary among institutions and eras. We conducted a multicenter retrospective study to investigate the prognostic factors for cytology-positive gastric cancer. We reviewed the medical records obtained from 6 institutions, covering 2000-2019. There were 128 patients with positive cytology and no other distant metastases that underwent R1 gastrectomy. Univariate and multivariate analyses to identify prognostic factors for overall survival were conducted using Cox's proportional hazards models. The median overall survival time was 18.6months. In univariate analyses, age (≥ 80years vs. < 70years), performance status (2, 3 vs. 0), prognostic nutritional index (< 35 vs. ≥ 40), the extent of lymphadenectomy (D1 vs. ≥ D2), macroscopic type (type 4 vs. non-type 4), and postoperative chemotherapy (none vs. S-1) were significantly correlated with worse survival. Multivariate analysis revealed that lymph node metastasis (pN3b vs. pN0, hazard ratio 4.46, 95% confidence interval 1.17-16.9, p = 0.03) and postoperative chemotherapy (none vs. S-1, hazard ratio 2.28, 95% confidence interval 1.16-4.45, p = 0.02) were independent risk factors for death. No postoperative chemotherapy regimen showed a survival benefit over S-1 monotherapy. Massive lymph node metastasis was an independent risk factor in cytology-positive gastric cancer. Postoperative chemotherapy was also an independent prognostic factor, though the most beneficial regimen was still uncertain.

Impact of preoperative chemotherapy as initial treatment for advanced gastric cancer with peritoneal metastasis limited to positive peritoneal lavage cytology (CY1) or localized peritoneal metastasis (P1a): a multi-institutional retrospective study.

Gastric cancer (GC) patients with peritoneal metastasis are defined as stage IV in the Japanese classification of GC. For patients with peritoneal metastasis limited to positive peritoneal lavage cytology (CY1) and/or localized peritoneal metastasis (P1a), gastrectomy followed by S1 monotherapy is one of the most widely accepted therapeutic strategy in Japan. This study investigated the efficacy of preoperative chemotherapy as initial treatment in GC patients with CY1 and/or P1a. We retrospectively reviewed GC patients diagnosed with CY1 and/or P1a at 34 institutions in Japan between 2008 and 2012. Selection criteria were: adenocarcinoma, no distant metastasis except CY1 or P1a, and no prior treatment. The subjects were divided into an Initial-Chemotherapy group and an Initial-Surgery group, according to the initial treatment. A total of 824 patients were collected and 713 eligible patients were identified for this study. As the initial treatment, 150 patients received chemotherapy (Initial-Cx), and 563 patients underwent surgery (Initial-Sx). Initial-Cx regimens were cisplatin plus S1/docetaxel plus cisplatin plus S1/others (n = 90/37/23). Both overall survival (OS) and progression-free survival (PFS) were similar between the Initial-Cx and Initial-Sx groups (median OS 24.8 and 24.0months, HR 1.07, 95% CI 0.87-1.3; median PFS 14.9 and 13.9months, HR 1.04, 95% CI 0.85-1.27). The 5-year OS rates were 22.3% in the Initial-Cx group and 21.5% in the Initial-Sx group. Although, the preoperative chemotherapy did not show a survival benefit for GC patients with CY1 and/or P1a, initial-Cx showed favorable survival in patients who converted to P0 and CY0.

Is it Necessary to Confirm Negative Margins in Gastrectomy for Peritoneal Lavage Cytology-positive Gastric Cancer?

The survival benefit of negative resection margins in patients who undergo gastrectomy with positive peritoneal lavage cytology (CY1) is unknown. We reviewed the medical records of 128 patients with CY1 but no other distant metastases who had undergone R1 gastrectomy, 21 of whom had positive margins. We compared overall survival (OS) according to margin status. The positive-margin group had poorer performance status scores (p=0.02), higher number of patients had undergone limited lymphadenectomy (p=0.01), had type 4 tumors (p=0.01), and undifferentiated type (p=0.02). Median OS was 19.0 and 16.9 months in the groups with negative and positive margins, respectively (HR=1.26, 95%CI=0.75-2.12, p=0.39). An inverse probability of treatment weighted analysis showed an OS of 13.1 and 11.9 months for the groups with negative and positive margins, respectively (HR=0.83, 95%CI=0.43-1.63, p=0.59). The prognoses of patients with CY1 and negative or positive margins may be equivalent.

Is the peritoneal lavage cytology coincided with peritoneal metastasis for gastric cancer?

e16533 Background: Gastric cancer (GC) with peritoneal metastasis (PM) is associated with a poor prognosis. The free cancer cells are the prerequisite of peritoneal metastasis. Peritoneal lavage cytology (PLC) is the main measure to identify the free cancer cells, but its positive rate is relatively low. This study aims to investigate the association between the result PLC and peritoneal metastasis for GC. Methods: From November 2017 to December 2019, 33 patients with GC were confirmed with PM through computerized tomography or diagnostic laparoscopy. The inflow and outflow catheters were inserted laparoscopically in all patients for postoperative hyperthermic intraperitoneal chemotherapy. PLC was performed with at least 200 ml of fluid and examined by measures of cytology and immunocytopathology. Ascites was aspirated if detected or 500 milliliter of normal saline infused the Douglas cavity, para-colic gutters and the right and left sub-phrenic cavity and then aspirated. Results: There were 15 males and 18 females and the median age was 56 (24-84) years old. All patients had a cT4a/cT4b and an N-positive tumor. The overall positive PLC (PLC+) rate was 63.6% (21/33). The distribution of Lauren classification was respectively 5 (15.2%) intestinal, 26 (78.8%) diffused and 2 (6.1%) mixed tumor. The diffused cases had a higher rate of PLC+ ( P = 0.004). All 5 intestinal GC had a negative PLC (PLC-). 71.4% (20/28) of patients with a grade G3/G4 had a PLC+, compared, no PLC+ was recorded in 5 grade G1/G2 patients (P = 0.003). The median peritoneal carcinomatosis index (PCI) was 14 (1-39). The PLC+ rate was 94.7% (18/19) in PCI &gt; = 10 group and 21.4% (3/14) in PCI &lt; 10 group ( P &lt; 0.001). The median ascites was 200 (0-7000) ml. The PLC+ rate was 88.2% 15/17) in ascites &gt; = 200 ml group and 37.5% (6/16) in ascites &lt; 10 ml ( P = 0.002). The median follow-up was 13(1-27) months and the overall survival was 75.8%, but no significance was detected between PLC+ group and PLC- group. Conclusions: The present study suggested that the result of PLC was not completely coincided with PM for GC by measures of cytology and immunocytopathology, especially for intestinal and grade G1/G2 tumor.

Multicenter retrospective observational study of pancreatic cancer with positive peritoneal lavage cytology intended for surgical resection.

695 Background: Although macroscopically curative resection has been performed for pancreatic cancer with positive peritoneal lavage cytology (CY1), the prognosis is poor in most reports. In 2013, the JASPAC01 trial showed that S-1 was superior to Gemcitabine (GEM) as adjuvant chemotherapy for resected pancreatic cancer, and S-1 was also administered to the patients with CY1 who had undergone macroscopically curative resection. Methods: This is a multicenter retrospective observational study that collected data of the patients with pancreatic adenocarcinoma who were diagnosed with CY1 between 2007 and 2015 and had no other noncurable factors. Results: One hundred twenty-seven patients were enrolled from 14 institutions, and 3 were excluded due to liver metastasis or non-adenocarcinoma. The median age was 67 years old and almost patients had PS 0 or 1. Of the 124 patients, 114 underwent macroscopically curative resection and the median overall survival (OS) and recurrence free survival (RFS) were 16.7 and 7.2 months. Of the resected patients, 80 (70%) had no early recurrence and started postoperative adjuvant chemotherapy. Adjuvant chemotherapy regimens were S-1 in 43 patients (54%), GEM in 31 (39%) and others in 6 (7%). The median OS was 21.0 months with S-1 and 19.2 months with GEM (HR: 0.73, 95%CI: 0.44-1.22, P = 0.23), whereas the median RFS was 10.2 and 7.1 months (HR: 0.58, 95%CI: 0.36-0.95, P = 0.03), respectively. Conclusions: After the report of JASPAC01, most patients with pancreatic cancer with CY1 received macroscopically curative resection and treated with S-1 as adjuvant therapy, however the efficacy was insufficient. We should consider appropriate treatment strategies for patients with pancreatic cancer with CY1 intended for surgical resection.

ASO Author Reflections: What Is the Best Treatment for Gastric Cancer with Positive Peritoneal Lavage Cytology or Localized Peritoneum Metastasis?

ASO Author Reflections: What Is the Best Treatment for Gastric Cancer with Positive Peritoneal Lavage Cytology or Localized Peritoneum Metastasis?

Meta-analysis of recurrence pattern after resection for pancreatic cancer

Initial recurrence mapping of resected pancreatic ductal adenocarcinoma (PDAC) could help in stratifying patient subpopulations for optimal postoperative follow-up. The aim of this systematic review and meta-analysis was to investigate the initial recurrence patterns of PDAC and to correlate them with clinicopathological factors. MEDLINE and Web of Science databases were searched systematically for studies reporting first recurrence patterns after PDAC resection. Data were extracted from the studies selected for inclusion. Pooled odds ratios (ORs) and 95 per cent confidence intervals were calculated to determine the clinicopathological factors related to the recurrence sites. The weighted average of median overall survival was calculated. Eighty-nine studies with 17 313 patients undergoing PDAC resection were included. The weighted median rates of initial recurrence were 20·8 per cent for locoregional sites, 26·5 per cent for liver, 11·4 per cent for lung and 13·5 per cent for peritoneal dissemination. The weighted median overall survival times were 19·8 months for locoregional recurrence, 15·0 months for liver recurrence, 30·4 months for lung recurrence and 14·1 months for peritoneal dissemination. Meta-analysis revealed that R1 (direct) resection (OR 2·21, 95 per cent c.i. 1·12 to 4·35), perineural invasion (OR 5·19, 2·79 to 9·64) and positive peritoneal lavage cytology (OR 5·29, 3·03 to 9·25) were significantly associated with peritoneal dissemination as initial recurrence site. Low grade of tumour differentiation was significantly associated with liver recurrence (OR 4·15, 1·71 to 10·07). Risk factors for recurrence patterns after surgery could be considered for specific surveillance and treatments for patients with pancreatic cancer.

Conversion therapy for peritoneal lavage cytology-positive type 4 and large type 3 gastric cancer patients selected as candidates for R0 resection by diagnostic staging laparoscopy.

The long-term outcomes of type 4 and large type 3 gastric cancer patients with positive peritoneal lavage cytology (CY1) remain unsatisfying. We evaluated our treatment strategy of conversion therapy for CY1 patients without peritoneal dissemination (P0). Diagnostic staging laparoscopy (DSL) was performed before treatment. Chemotherapy was applied for DSL-diagnosed P0CY1. The re-evaluation of peritoneal metastasis by staging laparoscopy (re-SL) was performed when a response to chemotherapy was identified by gastroscopy and/or CT. Gastrectomy with radical lymphadenectomy was applied as conversion therapy when peritoneal lavage cytology-negative (CY0) and P0 were diagnosed with re-SL, with the aim of achieving R0 resection. Chemotherapy was continued as palliative treatment in patients for whom re-SL was not applicable or when re-SL did not confirm P0CY0. The long-term outcomes were retrospectively evaluated. Between 2009 and 2015, 214 patients with type 4 and large type 3 gastric cancer underwent DSL in the Cancer Institute Hospital. Thirty-nine patients were initially diagnosed with P0CY1. Seven patients received palliative gastrectomy first due to outlet obstruction or other reasons. Thirty-two patients received chemotherapy first. Among them, 13 patients underwent gastrectomy as conversion therapy and 19 were treated with palliative chemotherapy. The 3-year survival rate of patients who underwent conversion therapy, palliative chemotherapy and palliative gastrectomy was 76.9% [95% confidence interval (CI) 47.8-92.4%], 10.5% (95% CI 1.9-42.3%), and 0%, respectively. Conversion therapy might be a promising treatment for P0CY1 type 4 and large type 3 gastric cancer patients. Re-SL was useful for selecting candidates for R0 resection.

A single-institution retrospective analysis of gastric carcinoma with positive peritoneal lavage cytology and without serosal invasion: A case series.

Background and objectivesPeritoneal dissemination of gastric cancer is often associated with serosal infiltration. The aim of this study was to evaluate the clinical importance of peritoneal lavage cytology in patients with gastric carcinoma without serosal invasion. The incidence and impact on prognosis of positive cytology were analyzed.MethodsOf 2768 patients with gastric cancer, outcomes and pathological characteristics of 973 patients were reviewed retrospectively. All patients underwent peritoneal lavage at laparotomy for curative or palliative resection of gastric cancer between 1999 and 2017. Among these, 479 who underwent surgery from January 1999 to March 2012 were also reviewed to analyze 5-year survival.ResultsOf 973 patients enrolled, 338 (35%) did not have serosal invasion, and peritoneal cytology was positive in 4/338 (1.2%). Of these four patients, one had submucosal invasion and three had muscularis propria invasion. Of 635 patients with serosal invasion, peritoneal cytology was positive in 74/635 (12%). Of 479 patients reviewed for survival, cytology was positive in 32/479, with 3/32 (9%) surviving for five years, and cytology was negative in 447 patients with 266/447 (60%) surviving for five years.ConclusionsCytologic evaluation should be routinely performed in patients with early-stage gastric cancer.

Role of positive peritoneal lavage cytology in carcinoma gall bladder: a prospective observational study of 60 patients with the preoperative diagnosis

Introduction: Positive peritoneal lavage cytology ( PLC) in patients with carcinoma stomach is considered M1 disease according to AJCC classification (7th edition, 2010). Status of PLC positivity in carcinoma gall bladder (CGB) is untested yet. Method: The study included 60 patients who underwent treatment in PGIMER, Chandigarh, India (June 2015–July 2016). After staging laparoscopy (SL), abdomen was explored and 50ml of normal saline instilled in the peritumoral region, right paracolic gutter and pelvis. The lavage fluid was aspirated, mixed with an anticoagulant and spun to obtain a sediment that was subjected to Liquid Based Cytology. Papanicolaou and May Grunwald Giemsa slides were studied for malignant cells. During SL, if metastatic, lavage was done laparoscopically. When resectable, patients underwent R0 resection. Results: There were 25 resectable, 2 unresectable, 22 metastatic and 11 cases of xanthogranulomatous cholecystitis. 6 out of 49 CGB patients had positive PLC ( 12.2%).1 patient had resectable G3pT2N0M0 adenocarcinoma, 1 had unresectable celiac lymph nodal metastasis and 4 had peritoneal metastasis on SL. The median disease- specific survival for metastatic disease was 4 months. The same for resected population (negative PLC) was not reached. The disease-free survival of the only resected patient with positive PLC was 5 months, comparable to that of metastatic patients. The survival difference between patients with positive and negative PLC was not significant. Conclusion: Although positive PLC may suggest advanced disease, the correlation between PLC and survival or disease stage is not statistically significant yet.

Multidisciplinary therapy for scirrhous gastric cancer: a retrospective analysis and proposal of new treatment strategy.

BackgroundScirrhous gastric cancer (SGC) is highly invasive and metastatic because of its interactions with stromal cells, such as fibroblasts and macrophages, and extracellular matrix, leading to a higher incidence of peritoneal metastasis (PM) than other gastric cancers (GCs). Taxane-based intraperitoneal chemotherapy (IPC) is a promising therapy for PM. We retrospectively analyzed outcomes of multidisciplinary therapies that included IPC for SGC.Patients and therapyOf 1,679 GC patients treated between 1990 and 2012, we analyzed 119 patients who underwent multidisciplinary therapy for SGC. Patients without PM received gastrectomy with lymphadenectomy and resection of involved adjacent organs followed by intraoperative IPC using cisplatin. Patients with PM received chemotherapy using fluorouracil, with or without methotrexate plus IPC using cisplatin before 2000, and S-1 plus IPC using paclitaxel or docetaxel since 2000.ResultsOf the 119 patients, 73 (61%) had PM and 63 (53%) had positive peritoneal lavage cytology. Of the 89 gastrectomy patients, 30 (34%) had macroscopic residual tumors (R2). Of the patients treated since 2000, 66 (100%) received S-1 plus taxanes and 44 patients (67%) received taxane-based IPC. Median survival time was significantly longer in the post-2000 group (22.8 months) than in the pre-2000 group (9.5 months). In univariate analysis, lavage cytology, PM, taxane-based IPC, gastrectomy, and R2 resection were significant prognostic factors. However, only R2 resection was an independent prognostic factor in multivariate analysis (hazard ratio: 5.53, 95% CI: 2.05–14.93).ConclusionAs use of taxane-based IPC is not an independent prognostic factor, new multidisciplinary therapies are necessary to avoid R2 resections.

Prognostic factors for cytology-positive gastric cancer

Positive peritoneal lavage cytology for gastric carcinoma cells (CY1) is considered distant metastasis and is classified as Stage IV. However, patients with CY1 comprise a heterogeneous population, and their prognosis varies greatly. The prognostic factors for gastric cancer patients with CY1 were retrospectively reviewed. The participants were 80 gastric cancer patients with CY1 in our institution encountered between 2005 and 2017. Prognostic factors were analyzed using univariate and multivariate analyses. The operative procedure was distal gastrectomy for 30 patients, total gastrectomy for 27 patients, staging laparoscopy for 10 patients, gastrojejunostomy for 8 patients, and probe laparotomy for 5 patients. Other distant metastases were recognized in 36 patients. A multivariate analysis revealed that other distant metastases were the strongest independent risk factor for the overall survival (p < 0.0001). When the cohort was limited to CY1 patients without other distant metastases, cN2-3 (p = 0.01), the prognostic nutritional index (PNI) < 40 (p = 0.02) and Type 4 (p = 0.03) were independent risk factors according to a multivariate analysis. The survivals of patients with cN2-3 or PNI < 40 after gastrectomy were equivalent to those with other distant metastases, as assessed by log-rank analyses. The prognoses of CY1 gastric cancer patients with cN2-3 or PNI < 40 were poor, even after gastrectomy.

Nuclear heat shock protein 110 expression is associated with poor prognosis and hyperthermo-chemotherapy resistance in gastric cancer patients with peritoneal metastasis.

AIMTo investigate the significance of heat shock protein 110 (HSP110) in gastric cancer (GC) patients with peritoneal metastasis undergoing hyperthermo-chemotherapy.METHODSPrimary GC patients (n = 14) with peritoneal metastasis or positive peritoneal lavage cytology who underwent distal or total gastrectomy between April 2000 and December 2011 were enrolled in this study. The patients underwent postoperative intraperitoneal hyperthermo-chemotherapy using a Thermotron RF-8 heating device two weeks after surgery. We analyzed nuclear HSP110 expression in surgically resected tumors using immunohistochemistry. Additionally, the effect of HSP110 suppression on hyptherthermo-chemosensitivity was assessed in vitro in the MKN45 GC cell line using the HSP inhibitor KNK437.RESULTSHSP110 immnohistochemical staining in 14 GC patients showed that five (35.7%) samples belonged to the low expression group, and nine (64.3%) samples belonged to the high expression group. Progression-free survival was significantly shorter in the HSP110 high-expression group than in the low-expression group (P = 0.0313). However, no significant relationships were identified between HSP110 expression and the clinicopathological characteristics of patients. Furthermore, high HSP110 expression was not an independent prognostic factor in GC patients with peritoneal metastasis (P = 0.0625). HSP110 expression in MKN45 cells was suppressed by KNK437 at the hyperthermic temperature of 43 °C in vitro. Comparison of MKN45 cell proliferation in the presence and absence of KNK437 at 43 °C, revealed that proliferation was significantly decreased when HSP110 was inhibited by KNK437. Additionally, HSP110 suppression via HSP inhibitor treatment increased cellular sensitivity to hyperthermo-chemotherapy in vitro.CONCLUSIONThe expression of nuclear HSP110 in GC patients might be a new marker of chemosensitivity and a therapeutic target for patients who are tolerant to existing hyperthermo-chemotherapies.

Is Pancreatic Head Cancer with Portal Venous Involvement Really Borderline Resectable? Appraisal of an Upfront Surgery Series.

It remains controversial whether the degree of venous involvement really is associated with borderline resectability of pancreatic cancer. A single-center retrospective review of patients who underwent upfront pancreaticoduodenectomy for T3 pancreatic cancer without arterial involvement was performed. The patients were classified as having resectable tumors without venous contact (R group), resectable tumors with venous contact of 180° or less (R-PV group), and borderline resectable tumors with venous contact greater than 180° (BR-PV group). The unresectable group included those who had unresected tumors with paraaortic lymph node metastasis, positive peritoneal lavage cytology, or locally advanced disease. The overall survival and prognostic factors were analyzed. The study enrolled 299 resected patients, including 141 patients in the R group, 119 patients in the R-PV group, and 39 patients in the BR-PV group. The overall survival did not differ significantly between the R-PV group and the BR-PV group (median survival, 20.7 vs 18.6months; P=0.807). Among the 158 patients who had tumors with venous contact, only a tumor size of 50mm or larger (P=0.041) was an independent prognostic factor in a multivariate analysis, and the overall survival for the patients with both venous contact and tumor size 50mm or larger was comparable with that for the unresectable group (P=0.547). The degree of venous involvement may not be associated with the resectability of pancreatic head cancer, whereas tumors 50mm in size or larger that develop venous invasion may be categorized as borderline resectable pancreatic cancers.

FBXO50 Enhances the Malignant Behavior of Gastric Cancer Cells.

Challenges to our understanding the molecular mechanisms of the progression of gastric cancer (GC) must be overcome to facilitate the identification of novel biomarkers and therapeutic targets. In this article, we analyzed the expression of the gene encoding F-box-only 50 (FBXO50) and determined whether it contributes to the malignant phenotype of GC. FBXO50 messenger RNA (mRNA) levels and copy numbers of the FBXO50 locus were determined in 10 GC cell lines and a nontumorigenic epithelial cell line. Polymerase chain reaction array analysis was performed to identify genes coordinately expressed with FBXO50. The effects of inhibiting FBXO50 on GC cell proliferation, adhesion, invasiveness, and migration were evaluated using a small interfering RNA targeted to FBXO50 mRNA. To evaluate the clinical significance of FBXO50 expression, we determined the levels of FBXO50 mRNA in tissues acquired from 200 patients with GC. The levels of FBXO50 mRNA were increased in five GC cell lines and positively correlated with those of ITGA5, ITGB1, MMP2, MSN, COL5A2, GNG11, and WNT5A. Copy number gain of the FBXO50 locus was detected in four GC cell lines. Inhibition of FBXO50 expression significantly decreased the proliferation, adhesion, migration, and invasiveness of GC cell lines. In clinical samples, high FBXO50 expression correlated with increased pT4, invasive growth, lymph node metastasis, and positive peritoneal lavage cytology. Patients with high FBXO50 expression had a significantly higher prevalence of recurrence after curative gastrectomy and were more likely to experience shorter overall survival. FBXO50 may represent a biomarker for GC phenotypes and as a target for therapy.

Intraoperative peritoneal lavage cytology offers prognostic significance for gastric cancer patients with curative resection.

Outcomes of patients with gastric cancer who exhibit positive peritoneal lavage cytology findings (CY +) vary by diagnostic methods because of quantitative and qualitative cancer cell diversity. This study sought to establish practical diagnostic criteria for performing curative resections, based on peritoneal lavage cytology findings in gastric cancer patients. We enrolled 1028 patients with gastric cancer who underwent R0/1 (n = 911) or R2 (n = 117) resections and analyzed relationships between cancer cell findings in peritoneal lavage fluid and clinicopathological factors in the R0/1 group. We found 68 patients with CY + status. Receiver operating characteristic analyses and multivariate analyses showed that the presence of ≥1 signet ring cell, ≥5 cell clusters or ≥50 isolated cancer cells in peritoneal lavage fluid predicted poor prognoses in the 68 CY + patients. High‐risk CY + group patients with at least one of the above predictors had the highest hazard ratio (HR = 3.28, P < 0.001). The remaining (low‐risk) patients had a survival curve similar to that of patients with a normal cytology. The high‐risk CY + patients who underwent R1 resection had poor prognoses despite no macroscopic peritoneal metastasis (2% 5‐year survival)—equivalent to that of patients who underwent R2 resection. The CY + criteria defined in this study could help identify candidates for curative resection as an initial therapy for gastric cancer.

Risk factors for latent distant organ metastasis detected by staging laparoscopy in patients with radiologically defined locally advanced pancreatic ductal adenocarcinoma.

We aimed to identify risk factors for latent distant organ metastasis in patients with radiographically defined locally advanced (RDLA) pancreatic ductal adenocarcinoma (PDAC). RDLA disease was defined as unresectable disease without distant organ metastasis based on resectability status by NCCN guidelines. Between January 2005 and November 2015, 110 consecutive patients underwent staging laparoscopy to rule out latent distant metastasis. Univariate and multivariate analyses were performed to identify risk factors for latent distant organ metastasis or peritoneal metastasis (PM), defined as peritoneal dissemination and/or positive peritoneal lavage cytology (PPC). Latent distant organ metastasis was diagnosed by staging laparoscopy in 62 patients. PPC was found in 23%, peritoneal dissemination in 19%, and liver metastasis in 15%. Univariate analysis showed tumor location, preoperative CA 19-9 level and tumor size, and multivariate analysis revealed tumor size >55mm and CA 19-9 level>60IU/ml as risk factors for latent distant metastasis. Multivariate analysis showed pancreas body-tail tumors and tumor size >42mm as risk factors for PM; 65.4% of pancreas body-tail tumors >42mm had PM. Patients with large pancreas body-tail tumors and high CA 19-9 level are at greater risk for latent distant organ metastasis or PM, and should undergo staging laparoscopy routinely for accurate diagnosis (UMIN000023125).