Incidence Of Peritoneal Metastasis Research Articles

Gender medicine in peritoneal diseases

Diseases of the peritoneum are divided into benign and malignant, whereby malignant diseases are more frequent. The incidence of peritoneal metastases is difficult to determine as they are frequently not listed separately in cancer databases and registries. Peritoneal metastases can be caused by many primary tumors but are particularly frequent in gastric, ovarian and colorectal carcinomas. Systemic chemotherapy shows gender-specific differences in the tolerability, especially gastrointestinal side effects and hematological toxicity occur more often in women. Surgical treatment options in selected patients include cytoreductive surgery with or without hyperthermic intraperitoneal chemoperfusion (HIPEC). The treatment recommendations depend on the primary tumor entity and the stage of the disease. Hysterectomy and/or salpingo-oophorectomy is often necessary during cytoreductive surgery. As the incidence of cancerous diseases is increasing in younger patients, the aspect of fertility is becoming increasingly more important. The iatrogenically induced menopause is another aspect that needs to be addressed after these types of procedures. Women with gastric and colorectal cancer tend to have aslightly better survival rate, especially in localized tumors; however, in advanced tumor stages the survival rates are comparable. Even if gender-specific differences in incidence, treatment response and adverse events are conspicuous, there is so far no exact explanation for these differences. More studies are needed in order to treat both genders as adequately as possible, with low adverse events and to achieve the best possible outcome.

CXCL8 and the peritoneal metastasis of ovarian and gastric cancer.

CXCL8 is the most representative chemokine produced autocrine or paracrine by tumor cells, endothelial cells and lymphocytes. It can play a key role in normal tissues and tumors by activating PI3K-Akt, PLC, JAK-STAT, and other signaling pathways after combining with CXCR1/2. The incidence of peritoneal metastasis in ovarian and gastric cancer is extremely high. The structure of the peritoneum and various peritoneal-related cells supports the peritoneal metastasis of cancers, which readily produces a poor prognosis, low 5-year survival rate, and the death of patients. Studies show that CXCL8 is excessively secreted in a variety of cancers. Thus, this paper will further elaborate on the mechanism of CXCL8 and the peritoneal metastasis of ovarian and gastric cancer to provide a theoretical basis for the proposal of new methods for the prevention, diagnosis, and treatment of cancer peritoneal metastasis.

Global multi-center phase I trial of the intraperitoneal infusion of anti-EpCAM x anti-CD3 bispecific antibody catumaxomab for advanced gastric carcinoma with peritoneal metastasis.

e16102 Background: Advanced gastric cancer (GC) patients (pts) have high incidence of peritoneal metastasis (PM), resulting in ascites, cachexia and poor life quality. EpCAM is highly expressed on GC but no on peritoneum. Catumaxomab intraperitoneal infusion (i.p.) was previously demonstrated to eradicate EpCAM+ cancers and control the malignant ascites in Europe (Heiss. Int. J. Cancer.2010). We present initial safety, pharmacokinetics (PK), and efficacy from the multi-center phase I trial of Catumaxomab on GC pts with PM in Asian population (NCT04222114). Methods: GC pts who had progressed on at least two prior standard systemic therapies with peritoneal metastasis were enrolled. Pts received Catumaxomab i.p. of 10 μg, 20 μg, 50 μg and 150 μg on days 1, 4, 8 and 11, respectively in the 1st cycle. From the 2nd cycle, Pts received Catumaxomab i.p. of 20 μg, 50 μg, 150 μg on days 1, 4 and 8, respectively. The cycle was 42 days in Cohort A, and 28 days in Cohort B. Catumaxomab PK were evaluated, tumor measurements and quantification of ascites by five-point method (Oriuchi, JJCO,2005) were performed Q6W. The primary endpoint was overall survival (OS); secondary endpoints were response rate of ascites, progression-free interval of peritoneal metastatic lesions and puncture-free survival (PuFS); Data cut-off date was Jan 29,2022. Results: 17 pts from 14 sites (median age: 52.5 yr, ECOG PS: 0 [n=2], 1 [n=14], 2[n=1], Cohort A:9, Cohort B:8) were treated. There were no dose-limiting toxicities (DLTs). The most common treatment-emergent adverse event (TEAE) was pyrexia (76.5%) and abdominal pain (58.8%). Grade ≥3 treatment related adverse events (TRAE) of abdominal pain (23.5%), bilirubin conjugated increased (23.5%), lymphocyte count decreased (17.6%), ALT increased (11.8%), and AST increased (11.8%) were reported. No treatment related death or neurotoxicity occurred in the study. Median overall survival was 102 days (95%CI: 38-166), with 10 (58.8%) deaths observed. For ascites, CR+PR was observed in 4 cases (33%), no PD case was reported. No therapeutic ascites drainage was recorded after cycle 1. Median PuFS was 116 days (95%CI: 28-157). Median progression-free interval of peritoneal metastatic lesions was 102 days (95%CI: 38-166). PK: Catumaxomab concentrations in plasma increased in a dose-dependent manner and were similar to Caucasian population in Europe. Conclusions: This clinical study indicated that multiple cycles of Catumaxomab i.p. were safe and well tolerated in Asian population. PK profile was similar. Early efficacy signals were promising, especially in pts with ascites, which will be further investigated in phase 3 study. Clinical trial information: NCT04222114.

Comparison of neoadjuvant chemotherapy and postoperative adjuvant chemotherapy in the treatment of Borrmann type IV gastric cancer.

e16064 Background: Borrmann type IV gastric cancer is highly malignant and prone to peritoneal metastasis, including peritoneal dissemination (P1) and positive peritoneal cytology (CY1) causing a dismal prognosis. This study is to compare the efficacy of neoadjuvant chemotherapy and postoperative adjuvant chemotherapy in patients with Borrmann type IV gastric cancer and analyze the prognostic factors of these patients. Methods: According to different therapies, patients diagnosed with Borrmann type IV gastric cancer in Zhejiang Cancer Hospital from June 2010 to June 2020, were divided into two groups: neoadjuvant chemotherapy group (NCT group) and non-neoadjuvant chemotherapy group (NNCT group). Both of two groups were subjected to the propensity score matching (PSM) at a ratio of 1:2 and then the treatment completion rate and overall survival (OS) time were analyzed. Results: A total of 240 cases were included after propensity score matching and 80 patients and 160 patients were enrolled in the NCT group and NNCT group, respectively. Neoadjuvant chemotherapy and postoperative adjuvant chemotherapy were based on platinum combined with fluorouracil. For the efficacy of treatment, R0 resection was performed on 92.2% patients in the NCT group and 88.1% in the NNCT group, but there was no statistical difference (P=0.463). 3-year survival rate was 35.0% in the NCT group compared with 29.4% in the NNCT group (P=0.427), and the 5-year survival rate was 28.7% and 25.6%, respectively (P=0.460). For patients with and without R0 resection, the 3-year survival rate was 34.3% and 7.4% (P<0.001), and the 5-year survival rate was 30.0% and 0%, respectively (P<0.001). Hyperthermic intraperitoneal chemotherapy (HIPEC) was conducted on 40 patients (16.7%), and the survival rate of HIPEC group was better than that of non-HIPEC group (3 year survival rate: 55.0% vs 26.5%, P=0.073; 5 year survival rate: 45.0% vs 23.0%, P=0.174), but the difference was not statistically significant. Conclusions: Borrmann type IV gastric cancer was characterized by poor differentiation and high incidence of peritoneal metastasis. The efficacy of the neoadjuvant chemotherapy based on platinum combined with fluorouracil is limited. A combination of HIPEC and system chemotherapy may effectively improve the prognosis of these patients.

Abstract 958: Effective targeting of pancreatic ductal adenocarcinoma metastases with an integrin αvβ6-targeting peptide-drug conjugate

Abstract Pancreatic ductal adenocarcinoma (PDAC) exhibits an extremely poor prognosis, with 5 year-survival rates <5%. This is due to a lack of effective therapies for the majority of patients, 65% of whom present with metastatic disease. Integrin αvβ6 is expressed in >80% of human PDAC tumors including their paired metastases but is not significantly expressed by healthy pancreas tissue. Thus, αvβ6 represents a promising therapeutic target. We previously developed the αvβ6-specific peptide-drug conjugate (PDC) SG3299, composed of the DNA-binding pyrrolobenzodiazepine (PBD)-based compound tesirine conjugated to the αvβ6-targeting peptide A20FMDV2. Relative to the non-targeting PDC SG3511, SG3299 showed anti-tumor efficacy against αvβ6-positive human PDAC xenografts in immunodeficient mouse models. The present study aimed to evaluate the efficacy of αvβ6-targeted therapy on primary tumors and metastases in an immunocompetent murine model of PDAC. We have previously reported that KPC (Kras-G12D P53-R172H Pdx1-Cre) transgenic mouse PDAC tumors do not express αvβ6, so we ectopically expressed murine integrin-β6 in the TB32043 KPC-derived PDAC cell line, creating the αvβ6-expressing line TB32043mb6S2. When injected orthotopically into immunocompetent C57BL/6 mice, TB32043mb6S2 cells produced primary pancreatic tumors with αvβ6-positive metastases to the liver, peritoneum, and lung. Mice injected orthotopically with TB32043mb6S2 cells exhibited increased primary tumor desmoplasia, increased incidence of peritoneal metastases (100% vs 20%, p<0.05) and decreased survival (median survival 27 vs 37.5 days, p=0.0233) relative to mice injected with αvβ6-negative TB32043 cells. When injected into the tail vein of C57BL/6 mice, αvβ6-positive TB32043mb6S2 cells exhibited significantly increased colonisation of the lungs relative to TB32043 cells (p<0.0001). These data indicate that αvβ6 expression increases PDAC cell metastatic propensity. SG3299 was 17-fold more effective (p<0.0001) for TB32043mb6S2 cells versus TB32043 cells in vitro, indicating αvβ6-selective killing of PDAC cells by our αvβ6-targeting PDC. Moreover, treatment of αvβ6-positive orthotopic tumors with the αvβ6-specific PDC SG3299 significantly increased survival relative to the non-targeting PDC SG3511 or saline control (median survival 48 days vs 26 days vs 25.5 days, p<0.0001). When mice bearing αvβ6-positive TB32043b6S2 lung metastases generated by tail vein injection were treated with SG3299 or SG3511, the SG3299 therapy significantly reduced metastatic tumor burden relative to SG3511 (p<0.05). Together, these data indicate that the peptide-drug conjugate SG3299 shows efficacy against both αvβ6-positive primary and αvβ6-positive secondary tumors in immunocompetent animals, providing a molecular-specific drug for the effective therapy of pancreatic cancer. Citation Format: Elizabeth R. Murray, Nicholas F. Brown, Philip Howard, Luke Masterson, Francesca Zammarchi, Patrick H. van Berkel, John F. Marshall. Effective targeting of pancreatic ductal adenocarcinoma metastases with an integrin αvβ6-targeting peptide-drug conjugate [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 958.

Treatment efficacy of ramucirumab-based chemotherapy in patients with alpha-fetoprotein producing gastric cancer (AFPGC).

389 Background: AFPGC is an aggressive subgroup of gastric cancer and is associated with a worsened survival because of a high incidence of liver metastasis. Ramucirumab-based chemotherapy is the standard treatment as a second line in advanced gastric cancer. Recently ramucirumab has showed survival benefit in hepatocellular carcinoma, but only those with higher AFP levels. However, the efficacy of ramucirumab in AFPGC is unknown. Methods: We retrospectively assessed 283 patients who received paclitaxel or nab-paclitaxel combined with ramucirumab between July 2015 and December 2018. AFPGC was defined when serum AFP levels were elevated and correlated with the disease state during treatment. Non-AFPGC was defined when serum AFP levels were normal when diagnosed. Other patients were excluded. Patients’ demographics, progression-free survival (PFS), overall survival (OS) and objective response rates (ORR) were compared between the two groups. Results: Among the 283 patients, 24 patients were AFPGC and 189 patients were non-AFPGC. AFPGC was associated with high incidences of intestinal histology (46%) and liver metastasis (63%), while AFPGC was associated with a low incidence of peritoneal metastasis (21%), compared with non-AFPGC. There was no significant difference in PFS and OS between the two groups. Median PFS were 5.4 (95%CI 3.6-6.7) months in AFPGC and 4.1 (3.7-5.1) months in non-AFPGC (HR 0.93 95%CI 0.60-1.46, p = 0.788), respectively. Median OS were 19.0 (95%CI 13.2-NA) months in AFPGC and 19.3 (17.9-20.1) months in non-AFPGC (HR 1.21 95%CI 0.70-2.10, p = 0.494), respectively. Regarding with ORR, AFPGC showed higher ORR with 52.6% (95%CI 30.2-75.1), while 37.3% (95%CI 26.4-48.3) in non-AFPGC (p = 0.296), although this was not statistically significant. Conclusions: Ramucirumab showed comparable survival and higher ORR in AFPGC than in non-AFPGC. Considering the generally poor prognosis of AFPGC, it is speculated that ramucirumab may have compensated for disadvantage in survival.

Peritoneal metastasis after emergency hepatectomy and delayed hepatectomy for spontaneous rupture of hepatocellular carcinoma

Delayed hepatectomy is the preferred approach for spontaneous rupture of resectable hepatocellular carcinoma (HCC). However, delayed surgery for ruptured HCC may increase the risk of peritoneal metastasis. A retrospective analysis was conducted on the pooled data obtained from 44 HCC patients with spontaneously ruptured hemorrhage, These patients were divided into emergency group and delayed group. Perioperative events, overall survival (OS) and disease-free survival (DFS) rates, and the incidence of recurrent and metastatic disease were compared between these two groups. Median survival time was 17.0 months in the emergency group vs. 28.0 months in the delayed group. In the emergency group, the 6-month, 1-year and 3-year OS rates were 58.8%, 57.6% and 11.5%. In the delayed hepatectomy group, the 6-month, 1-year and 3-year OS rates of were 84.3%, 77.5% and 37.8%. The incidence of peritoneal metastasis was higher in delayed group than in the emergency group, but the difference was not statistically significant (40.7% vs. 35.3%, P>0.05). Delayed hepatectomy warrants better short-term prognosis, compared with emergency hepatectomy, for HCC patients with spontaneously ruptured hemorrhage. Delayed hepatectomy does not increase the possibility of postoperative peritoneal metastasis.

Attaching importance to diagnosis and treatment of peritoneal metastases from colorectal cancer

Peritoneal metastasis from colorectal cancer (CRC) are generally considered to be end-stage disease of CRC, which has greatly impacted the prognosis and quality of life of patients. In recent years, cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy following systemic control has gradually been accepted for the treatment of peritoneal metastasis from CRC. Unfortunately, it has not widely used in clinical practice for the reasons of instruments, experience, surgical complexity, postoperative complications and cost-effectiveness. There is still no sufficient importance attached to CRC with peritoneal metastasis. Researches on the mechanism and treatment of peritoneal metastasis should be encouraged. Screening of high risk patients for early intervention to reduce incidence of peritoneal metastasis, selecting effective regimens and exploring optimal model for patients with other distal metastasis to improve the outcome of patients may be of importance. Key words: Colonic neoplasms; Rectal neoplasms; Peritoneal metastasis, colorectal cancer; Cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy; Individualized treatment

Effectiveness and limitations of staging laparoscopy for peritoneal metastases in advanced gastric cancer from the results of JCOG0501: A randomized trial of gastrectomy with or without neoadjuvant chemotherapy for type 4 or large type 3 gastric cancer.

9 Background: In type 4 or large type 3 gastric cancer diagnosed as not having distant metastasis by imaging modalities, the incidence of peritoneal metastasis that was unexpectedly found during laparotomy was approximately 40%. Staging laparoscopy (SL) is a valuable method used for staging gastric cancer. This study aimed to clarify the effectiveness and limitations of SL for patients (pts) with type 4 or large type 3 gastric cancer. Methods: JCOG0501 is a randomized phase III trial of gastrectomy with or without neoadjuvant S-1 plus cisplatin for treating type 4 or large type 3 gastric cancer. Eligibility criteria included histologically proven gastric adenocarcinoma that was clinically type 4 or large type 3 gastric cancer and was diagnosed as R0/1-resectable using SL. Pts who underwent gastrectomy without neoadjuvant chemotherapy were included in this study. Results: In total, 316 pts (158 pts with and without neoadjuvant chemotherapy each) were enrolled between October 2005 and July 2013 from 44 institutions. Of the 158 pts without neoadjuvant therapy, 2 pts did not receive laparotomy. The remaining 156 pts were included in this analysis. Among them, except for 1 patient (P1), none were diagnosed with peritoneal metastases (P0) during SL. Among these 155 pts, 24 (15.5%) were diagnosed with peritoneal metastases at subsequent laparotomies (false-negative). Most of the overlooked peritoneal disseminated nodules were located in the intestinal mesentery (8 pts), transverse mesocolon (5 pts), or omental bursa (3 pts). The total number of peritoneal disseminated nodules at laparotomy was often ≤ 9 (1–3 nodules in 14 pts, 4–9 in 4 pts). Of the 156 included pts, 142 underwent R0/1-resection (91.0%) because some overlooked nodules were curatively resected. Conclusions: SL is a useful diagnostic tool to plan the management of type 4 and large type 3 gastric cancers, although the high false-negative rate cannot be ignored. In SL, detailed exploration of the mesentery, mesocolon, and omental bursa is recommended.

PWE-284 Signet ring colorectal carcinoma (SRCC): do we need to improve the treatment algorithm?

Introduction SRCC is an aggressive variant affecting younger population and has poorer prognosis. The literature explaining the biology as well as the optimum treatment algorithm of this particular variant is scarce due to its low incidence. Here, we present our experience about this peculiar variant from a tertiary cancer centre from India (Tata Memorial Centre, Mumbai). Method It’s a retrospective study (2011–2014) of all patients diagnosed with SRCC with department of gastro-intestinal oncology. SRCC was defined as per WHO criteria (adenocarcinoma with more than 50% of signet-ring cells). Peritoneal metastases or recurrences constituted peritoneal deposits, malignant ascites, omental deposits, ovarian deposits. SPSS-20 was used for statistical calculation. Results 170 consecutive patients with SRCC were diagnosed. It constituted 11.4% of all colorectal cases (170/1487). Median Age of the cohort was 41 years. Male to female ratio was 1.8:1. Most common location was recto-sigmoid area (Rectum: 41.2% and Sigmoid: 13.5%). Majority patients presented in stage III (51.8%) and stage IV (39.4%). Most of the stage IV patients had isolated peritoneal metastases (58/67, 86.5%). Colonic tumours, as compared to rectal tumours had higher incidence of peritoneal metastases (83.3% v/s 91.4%, p = 0.074) as well as isolated peritoneal recurrences (20.5% v/s 37.5%, p = 0.062). Most patients had high nodal burden (pN2: 57.9%). Curative therapy was feasible only in 56.47% (79/170) patients. 36.7% patients recurred after curative surgery. Amongst them 65.5% patients had isolated peritoneal recurrences. Amongst rectal cases, pathological complete response after NACTRT was seen in 21.6% (8/37) patients. Circumferential resection margin (CRM) was involved in 17.9% (7/39) patients. Median follow up was 17.4 months. Median relapse free survival (RFS) and overall survival (OS) of the cohort were 14.9 and 18.13 months respectively. OS of peritoneal and non-peritoneal metastases were equivalent (16 v/s 13months; p = 0.729). CRM involvement was associated with poorer RFS (15 months v/s 37.2 months; p = 0.060) and OS (19.9 months v/s 41.5 months; p = 0.018). Colonic primaries were associated with poorer OS than rectal tumours after curative resection (32.298 months v/s 40.089 months, p = 0.058) and RFS (24.74 months v/s 34.02 months; p = 0.048). Conclusion SRCC affects young patients and has predilection for peritoneal dissemination. More aggressive and/or extended chemotherapy schedules as well as prophylactic HIPEC at the time of primary surgery, especially for colonic tumours, should be attempted in a randomised control trial setting in order to improve dismal survival in these patients. Disclosure of interest None Declared.

Characteristics and prognosis of mucinous gastric carcinoma.

Mucinous gastric carcinoma (MGC) is a rare histological subtype of undifferentiated gastric carcinoma, accounting for ~2.6-6.6% of all gastric cancer cases. The clinicopathological characteristics and prognosis of MGC are controversial. The present study aimed to determine the clinicopathological characteristics and prognosis of patients with MGC. We retrospectively compared the characteristics and postoperative survival of 70 patients with MGC and 2,492 non-MGC (NMGC) cases who underwent surgical resection between 1990 and 2010. MGC was characterised by larger tumor size, macroscopic Borrmann type 2 and 3, T4 invasion of the gastric wall, positive N2 and N3 lymph node metastasis, positive lymphatic vessel invasion, positive venous invasion, peritoneal metastasis and advanced tumor stage III and IV. The prognosis of MGC patients was worse compared to that of NMGC patients, as the former group consisted of more advanced-stage cases. When patients with similar disease stages were compared, the incidence of peritoneal metastasis was significantly higher among MGC patients. However, hepatic metastasis was found significantly more often in NMGC patients. Otherwise, the prognosis of MGC and NMGC patients with similar disease stages was not significantly different. Therefore, our findings indicated that, although MGC is more rare and mostly detected at an advanced stage, the diagnosis of the mucinous histological subtype was not an independent prognostic factor.

Predictive value of CA125 in peritoneal metastasis and prognosis of patients with gastric carcinoma

To investigate the predictive value of serum CA125 in peritoneal metastasis, and to examine the association of CA125 with the prognosis. Clinical data of 1285 gastric cancer patients admitted to the Qilu Hospital from March 2003 to September 2008 were retrospectively reviewed. The sensitivity, specificity and accuracy of serum CA125 for peritoneal metastasis were analyzed. Clinicopathological characteristics and survival were compared between patients with normal serum CA125 level(≤35 μg/L) and patients with elevated serum CA125 level(>35 μg/L). The specificity, sensitivity and accuracy of serum CA125 for peritoneal metastasis were 96.0%, 13.8% and 81.2%, respectively. A significantly higher incidence of peritoneal metastasis was observed in the patients with elevated serum CA125 level as compared to those with normal serum CA125 level(43.2% vs. 16.5%). CA125 was an independent predictor of peritoneal metastasis(RR=3.475, 95% CI:2.124-5.685). The 5-year overall survival rate in patients with elevated serum CA125 level was 13.5%, which was significantly lower than that of patients with normal serum CA125 level (49.8%, P<0.01). CA125 was an independent prognostic factor of gastric cancers(HR=2.049, 95%CI:1.355-2.873). Serum CA125 is useful in predicting peritoneal metastasis and prognosis of gastric cancer, which should be used as a routine examination of gastric cancer patients.

The role of staging laparoscopy in type 4 gastric cancer.

35 Background: In type 4 gastric cancer, the incidence of peritoneal metastasis which was unexpectedly found during surgery was as high as 40 percent. It is very difficult to detect peritoneal metastasis in clinical imaging such as computed tomography or ultrasound before operation. Staging laparoscopy (SL) is considered to be an only minimal invasive procedure to detect peritoneal metastasis. However, the significance of SL had not yet been fully elucidated. The aim of this study is to assess the role of SL in type 4 gastric cancer. Methods: From September 2002 to March 2012, a total of 169 patients with type 4 gastric cancer who were diagnosed as not having distant metastasis in clinical imaging were enrolled in this study. SL was performed for 56 patients, and the other 113 patients underwent open laparotomy (OL) without SL. We retrospectively examined the incidence of peritoneal metastasis and positive peritoneal cytology and treatment courses in patients who underwent SL and OL. Results: In 56 patients undergoing SL, 23 (41%) had peritoneal metastasis and 40 (71%) had positive peritoneal cytology. Similarly, 54 (48%) had peritoneal metastasis and 86 (76%) had positive peritoneal cytology in 113 patients undergoing OL. There were no significant differences of the incidence of peritoneal metastasis and positive peritoneal cytology between the two groups. Subsequent treatments after SL or OL were diverse depends on patients condition and participating clinical trials, however, 17 (32%) in SL group and 13 (12%) in OL group were treated without surgical interventions. There was no morbidity and mortality in both SL group and OL group. In SL group, open surgery was performed soon afterword in 39 patients. Among them, 2 patients was failed to detect peritoneal metastasis by SL. Therefore the accuracy of detecting peritoneal metastasis in SL was 23/25 (92%). Conclusions: In type 4 gastric cancer, the incidence of peritoneal metastasis was around 40% and positive peritoneal lavage cytology was around 70% in both SL and OL. As SL is less invasive than OL, SL appears to be a useful way to detect peritoneal seeding and establish treatment strategy in patients with type 4 gastric cancer.

Factors associated with peritoneal metastasis in non-serosa-invasive gastric cancer: a retrospective study of a prospectively-collected database

BackgroundPeritoneal dissemination is the most common type of recurrence in advanced gastric cancer. The main mechanism is thought to be via the exfoliation of free cancer cells (FCCs) from tumor in the gastric serosa. The frequency of recurrence thus increases once the tumor cells penetrate the serosa. However, this type of recurrence also occurs in patients without serosal invasion, though the mechanisms responsible for have not been fully established. We therefore investigated the factors associated with peritoneal dissemination in patients with non-serosa-invasive gastric cancer.MethodsA total of 685 patients with non-serosa-invasive gastric cancer who underwent curative resection with retrieval of more than 15 nodes were selected. The associations between clinicopathological features and peritoneal dissemination were analyzed. Among them, the tumor infiltrating growth pattern (INF) were classified into α, β and γ according to the Japanese Classification of Gastric Carcinoma (JCGC).ResultsThe overall incidence of peritoneal metastasis was 20% (137/685). Age, Borrmann type, differentiation, INF, nodal status and free cancer cells (FCCs) were correlated with peritoneal dissemination using univariate analysis. However, only INF, Borrmann type and TNM node stage were identified as independent correlated factors with peritoneal metastasis by multivariate analysis when FCCs were excluded, and these were also prognostic factors. Peritoneal dissemination was more common in patients with INFγ, Borrmann III/IV and N3 stage. Among patients without FCCs, nodal involvement or vessel invasion, only INF remained an independent associated factor according to multivariate analysis.ConclusionsTumor infiltrating growth pattern (INF), together with Borrmann type and TNM node stage, are important factors associated with peritoneal metastasis in non-serosa-invasive gastric cancer.

Trans-peritoneal fine needle aspiration biopsy of hilar cholangiocarcinoma is associated with disease dissemination

BackgroundHilar cholangiocarcinoma presents both diagnostic and therapeutic challenges. While establishing a diagnosis is important for patients considering aggressive treatment, a transperitoneal fine needle aspiration (FNA) may lead to seeding of the tumour. The aim of the present study was to determine whether patients who have undergone transperitoneal FNA of the primary tumour have a higher incidence of metastases. Patients and MethodsOutcomes of 191 patients enrolled in a neoadjuvant chemoradiotherapy followed by liver transplantation (LT) from 1 October 1992 to 1 January 2010 were analysed. The incidence of metastases was compared between those who did or did not undergo a transperitoneal FNA biopsy of the primary tumour. ResultsA total of 16 patients underwent FNA biopsy. There were six patients with biopsies positive for adenocarcinoma and 5/6 (83%) had peritoneal metastases at operative staging. Nine patients had biopsies, which did not demonstrate a tumour, and had no evidence of metastasis. One patient had an equivocal biopsy. Of those who did not undergo a transperitoneal biopsy, the incidence of peritoneal metastasis was 8% (14/175), P= 0.0097 vs. positive staging (83%) in those with a diagnostic transperitoneal FNA. Survival at 5 years for those who underwent LT was 74%. ConclusionTransperitoneal biopsy of hilar cholangiocarcinoma is associated with a higher rate of peritoneal metastases, and it should not be performed if a curative approach such as LT is available.

Time to Death and Pattern of Death in Recurrence following Curative Resection of Gastric Carcinoma: Analysis Based on Depth of Invasion

It is difficult to predict recurrence in patients who undergo curative gastrectomy for gastric carcinoma. If the timing and site of recurrence can be predicted, it becomes easier to detect recurrent disease. Records of 290 patients who died of tumor recurrence after curative gastrectomy for gastric carcinoma were retrospectively analyzed to determine whether the depth of carcinoma invasion is independently correlated with the time to death due to tumor recurrence. Additionally, the relation between the pattern of recurrence and the depth of invasion of the gastric wall was examined. Postoperative survival in patients with tumors with deep invasion was shorter than that of patients with tumors with shallow invasion. Depth of invasion was a predictor of survival on multivariate analysis. When carcinoma invaded into deeper layers, the incidence of peritoneal metastasis and local recurrence rose and that of hematogenous metastasis fell. In conclusion, the timing of death and the site of recurrence after gastrectomy for gastric carcinoma might be predicted by the depth of invasion of the gastric wall.

Metastatic mode and DNA ploidy in gastric carcinoma.

We studied the amounts of nuclear DNA in gastric cancer metastases histologically and cytochemically by flow cytometry, which was performed retrospectively on paraffin-embedded specimens from 95 patients. At surgery, all cases of aneuploid cancer were positive for lymph node metastases. Liver metastases were frequently seen in aneuploid cancer (63%, P < 0.01), while lung metastases were the most common in diploid cancer (50%, P < 0.05). The incidence of peritoneal metastasis was high in undifferentiated diploid cancer (72%, P < 0.01). Local lymph node recurrence after surgery was more common in aneuploid than in diploid cancer (P < 0.01). The incidence of bone and distant lymph node metastasis was found to be strongly dependent on tissue differentiation. The DNA ploidy pattern is thus considered to be closely linked to lymph node, liver, and lung metastases in gastric cancer.

Proliferation-associated nuclear antigen p105 as a marker for metastasis of human gastric cancer

The expression of the proliferation-associated nuclear antigen p105 in 43 patients with advanced gastric carcinoma was studied by multiparameter flow cytometry. The p105 immunofluorescence intensity of tumor cells in the G0G1 phase was 1.8-14.5 times that in stromal cells, and the stromal cells could be separated by flow cytometry. The p105 intensity, which is the ratio of the mean fluorescence intensity of cancer cells to that of stromal cells in the G0G1 phase, was not correlated with the DNA index, the size of the S-phase fraction, or the histological type of the tumor. However, the intensity was significantly greater in patients with hepatic metastasis and significantly lower in patients with peritoneal metastasis. The patients with a p105 intensity of 4.0 or more had a significantly higher incidence of hepatic metastasis (8/22; 36%). The patients with a p105 intensity of less than 4.0 had a significantly higher incidence of peritoneal metastasis (8/21; 38%). These results suggest that the p105 intensity is a marker of metastasis useful in the treatment and follow-up of patients.