Linitis Plastica Type Research Articles

Randomized phase II study comparing neoadjuvant FLOT versus DOS for patients with type 4 or large type 3 gastric cancer (JCOG2204).

TPS418 Background: A randomized phase III trial (JCOG0501) failed to demonstrate a survival advantage of neoadjuvant chemotherapy with S-1 plus cisplatin (SP) for patients with resectable macroscopic type 4 and large type 3 gastric cancer (GC). Currently, initial resection followed by adjuvant chemotherapy is performed as the standard treatment for this population as well as general type GC in Japan. However, macroscopic type 4 and large type 3, mostly overlapping with scirrhous or linitis plastica type, have distinctive natures in age, dominant histology and metastatic site, exhibiting unfavorable prognosis after surgery with curative intent. Further therapeutic development using peri-operative chemotherapy is urgently desired for the improvement of this hard-to-treat subset of GC. Based on the successful results of the FLOT4 trial and PRODIGY trial, FLOT (5-fluorouracil/leucovorin/oxaliplatin/docetaxel) and DOS (docetaxel/oxaliplatin/S-1) will be anticipated to offer more potent efficacy compared to platinum doublet. However, it remains unclear which of these two regimens should be selected as a test arm of future phase III confirming efficacy of neoadjuvant chemotherapy in Japan. Methods: JCOG2204 is a multi-center, randomized phase II trial comparing neoadjuvant chemotherapy with FLOT (5-fluorouracil/levofolinate/oxaliplatin/docetaxel) versus DOS for resectable type 4 and large type 3 GC. This trial adopted the selection design to determine the most promising regimen for the subsequent phase III trial. Patients with histologically confirmed adenocarcinoma of the stomach, presenting with macroscopic type 4 or larger lesions (≥8 cm) of type 3, are eligible for this trial. Prior to registration, it is required to confirm the absence of non-curable factors other than positive lavage cytology (CY1) or peritoneal dissemination localized around the stomach (P1a) in a staging laparoscopy. Neoadjuvant FLOT arm consist of 4 courses of oxaliplatin (85 mg/m2) and docetaxel (50 mg/m²) with levofolinate (200 mg/m2) IV infusion for 1-2 hours, then 5-FU (2600 mg/m2, civ) for 24 hours on day 1, biweekly. Neoadjuvant DOS arm consists of 3 courses of oxaliplatin (100 mg/m2) and docetaxel (40 mg/m2) IV infusion for 1-2 hours on day 1, followed by oral S-1 80–120 mg/m2/day for 2 weeks (days 1–14), in a 3-week cycle. Adjuvant chemotherapy is performed according to the pathological TNM stage. A sample size was calculated based on Simon’s selection design assuming that a proportion of patients achieving pathological response Grade 1b or higher will be 65% in the superior regimen, 10% higher than 55% in the other. A total of 76 patients, which are required to ensure at least an 80% probability of correct selection, are planned to be enrolled over 2 years. Enrollment in JCOG2204 begun on 14th July, 2023 and clinical trial information is available in Japan Registry of Clinical Trials (jRCTs031230231). Clinical trial information: jRCTs031230231 .

Randomized phase II study comparing neoadjuvant 5-fluorouracil/oxaliplatin/docetaxel versus docetaxel/oxaliplatin/S-1 for patients with type 4 or large type 3 gastric cancer.

Macroscopic type 4 and large type 3 gastric cancer, mostly overlapping with scirrhous or linitis plastica type, exhibita highly invasive nature and showunfavorable prognosis after curative surgery, even with adjuvant chemotherapy. A randomized phase III trial (JCOG0501) failed to demonstrate a survival advantage of neoadjuvant chemotherapy with S-1 plus cisplatin for this population. The current authorsinitiated a randomized phase II study comparing neoadjuvant chemotherapy with 5-fluorouracil/oxaliplatin/docetaxelversus docetaxel/oxaliplatin/S-1for type 4 and large type 3 gastric cancer. 76 patients are planned to be enrolled over twoyears. The primary end point is the proportion of patients with a pathological response (grade 1b or higher)and secondary end points include overall survival and adverse events. Clinical Trial Registration: jRCTs031230231 (rctportal.niph.go.jp).

A phase II study of preoperative chemotherapy with docetaxel, oxaliplatin, and S-1 followed by gastrectomy with D2 plus para-aortic nodal dissection for gastric cancer with extensive lymph node metastasis: JCOG1704.

354 Background: Prognosis of gastric cancer (GC) with extensive lymph node metastasis (ELM) is poor due to unresectability even without distant metastases. We conducted a phase II study to evaluate the safety and efficacy of preoperative chemotherapy with docetaxel (D), oxaliplatin (O), and S-1 (S) followed by extended gastrectomy. Methods: Eligibility criteria included histologically proven adenocarcinoma of the stomach; bulky nodal involvement around major branched arteries to the stomach (Bulky N) and/or para-aortic nodal metastases (PAN); cM0 (except para-aortic nodes); negative lavage cytology; not linitis plastica type; PS of 0 or 1; 20-75 years old. Patients received three 21-day cycles of preoperative chemotherapy of D (40 mg/m2 on day 1), O (100 mg/m2 on day 1), and S (80-120 mg /body from day 1 to day 14), and then underwent gastrectomy with D2 plus para-aortic nodal dissection. After surgery, patients received adjuvant chemotherapy with S-1 for 1 year. Primary endpoint was major pathological response rate, defined by the disappearance of more than two-thirds of the primary tumor. Expected and threshold value of major pathological response was set at 40% and 25%, respectively. Sample size was calculated to be 50 based on a one-sided alpha of 0.1, power of 0.8 and single-arm phase II study using a Southwest Oncology Group (SWOG) two-stage design. Results: Between Oct 2018 and Mar 2022, 47 patients were enrolled, of whom 46 were eligible for efficacy analysis. The median age was 67 years. The pathological type was differentiated in 33 patients and undifferentiated in 14. Twenty patients had only bulky N, 17 had only PAN, and 10 had both of bulky N and PAN. Clinical stage was III in 19 and IV in 28 patients. Except one patient refused chemotherapy, 46 patients (45 in three cycles and 1 in one cycle) completed preoperative DOS. Forty-four patients (94%) underwent gastrectomy, including 23 distal gastrectomy and 21 total gastrectomy, and 43 (91%) had an R0 resection. Major pathological response was confirmed in 26 of 46 patients (57% with 80% CI: 46-67), including pCR of 24%, which met the statistical significance (p<0.0001). According to the Becker’s criteria, grade 3 was 13, grade 2 was 12, grade 1b was 7, and grade 1a was 11. DOS-related grade 3/4 toxicities included neutropenia in 11 patients (24%), anorexia in 7 (16%), diarrhea in 4 (9%), and febrile neutropenia in 4 (9%). Surgery-related grade 3/4 toxicities were abdominal abscess in 5 (12%) and pancreatic fistula in 3 (7%). No treatment-related death was observed. Conclusions: Preoperative DOS followed by gastrectomy with D2 plus para-aortic nodal dissection is safe, feasible, and effective for GC with ELM. Clinical trial information: jRCTs031180028 .

Neoadjuvant chemotherapy plus surgery for high-risk advanced gastric cancer: Long-term results of KDOG1001 trial.

4521 Background: In the phase 2, open-label, KDOG1001 (UMIN000003642) study, neoadjuvant chemotherapy (NAC) with docetaxel, cisplatin, and S-1 (DCS), followed by gastrectomy with D2 lymph node dissection for high-risk advanced gastric cancer showed feasibility of DCS therapy with an enough R0 resection rate of 90%. Here we present long-term results after a minimum follow-up of 3 years. Methods: Patients with bulky node metastasis (bulky N), linitis plastica (type 4), or large ulcero-invasive-type tumors (type 3) received up to four 28-day cycles of DCS neoadjuvant chemotherapy (docetaxel at 40 mg/m2, cisplatin at 60 mg/m2 on day 1, and S-1 at 40 mg/m2 twice daily for 2 weeks) followed by gastrectomy with D2 lymphadenectomy. This analysis presents the final preplanned assessment of outcomes after 3 years. Primary endpoint was R0 resection rate. Secondary endpoints included overall survival (OS), progression free survival (PFS), completion rate of the protocol treatment, and pathological response rate (pRR) of DCS NAC. Results: Of 40 patients enrolled from May 2010 through January 2017, 7 (17.5%) had bulky N, 18 (45.0%) had type 4, and 16 (40%) had large type 3 with 1 (2.5%) having both large type 3 and bulky N2. All included patients underwent preoperative DCS chemotherapy followed by surgery with D2 lymphadenectomy with 32 (80%) completed postoperative S-1 therapy for 1 year. After a median follow-up for surviving patients of 67 mo (range, 36 mo to 110 mo) at the last follow-up in January 2020, 3-year OS was 78% [95% confidence interval (CI) 62–88%], while 3-year PFS was 63% (95% CI 47–76%). Completion rate of the protocol treatment was 62.5% (25/40) with pRR of 57.5% (23/40). In bulky N2, 3-y OS was 86% and 3-y PFS was 71% with pRR of 100%. In type 4, 3-y OS was 67% and 3-y PFS was 50% with pRR of 44%. In large type 3, 3-y OS was 88% and 3-y PFS was 75% with pRR of 56%. Patients with type 4 had significantly worse OS and PFS than those with the other types [HR 7.20 (95% CI 2.23–32.21) and HR 3.00 (95% CI 1.21–8.19)]. Conclusions: Preoperative chemotherapy with up to four cycles of DCS followed by gastrectomy plus adjuvant S-1 therapy is a promising treatment strategy for patients with bulky node metastasis, type 4 and large type 3 gastric cancers. For type 4 cancer, further improvement of treatment strategy is needed. Clinical trial information: 000003642 .

Impact of adjuvant chemotherapy with S-1 on survival in patients with type 4 and large type 3 gastric cancer.

98 Background: The prognosis of patients with linitis plastica (type 4) and large ulcero-invasive-type (type 3) gastric cancer is reported to be extremely poor. In stage II/III gastric cancer, adjuvant chemotherapy with S-1 is a standard treatment in Japan. However, the efficacy of postoperative chemotherapy with S-1 in these types of patients with dismal prognosis is unknown. The aim of this study is to evaluate the impact of adjuvant chemotherapy with S-1 on survival in type 4 and large type 3 gastric cancer patients. Methods: A total of 152 patients with clinically resectable type 4 and large type 3 gastric cancer who underwent R0 or R1 surgery from 2002 to 2014 were included. The survival outcome between patents with surgery alone and patients who received adjuvant S-1 was compared using a 1:1 propensity score matching method. Results: Patients with adjuvant S-1 were significantly younger (67 vs 74 y, p = 0.009), had higher incidence of T4 (90 vs 62%, p < 0.001), N2-3 (84 vs 63%, p = 0.008), and cytology positive (52 vs 29%, p = 0.006) than in surgery alone patients. Before matching, median survival time (MST) was not different in surgery alone (n = 52) and adjuvant S-1 (n = 100) (31.3 vs 35.8 months, p = 0.41). Propensity score matching yielded 48 patients (24 patients in each group). After matching, baseline characteristics were well balanced between the two groups. Survival in patients with adjuvant S-1 was significantly better than in surgery alone patients (MST: 50.3 vs 15.4 months, p = 0.002). Cox proportional hazard analysis revealed adjuvant S-1 treatment was selected as independent prognostic factor (HR: 0.38, 95%CI: 0.18-0.76, p = 0.006), as well as lavage cytology (HR: 3.9, 95%CI: 1.8-8.9, p < 0.001). Conclusions: Adjuvant chemotherapy with S-1 may have a strong impact on survival in type 4 and large type 3 gastric cancer patients. The efficacy of this treatment will be further demonstrated in the future clinical trials.

Mo1209 Clinicopathologic Characteristics and Prognosis of Linitis Plastica Type and Localized Scirrhous Type of Gastric Cancer

Mo1209 Clinicopathologic Characteristics and Prognosis of Linitis Plastica Type and Localized Scirrhous Type of Gastric Cancer

Borrmann Type 4 Advanced Gastric Cancer: Focus on the Development of Scirrhous Gastric Cancer.

Early diagnosis of Borrmann type 4 advanced gastric cancer (AGC) is very important for improving the prognosis of AGC patients. Because there is no definite mass in most cases of Borrmann type 4 AGC, its accurate diagnosis via endoscopy requires an understanding of its pathogenesis and developmental process. Moreover, many people confuse linitis plastica (LP) type gastric cancer (GC), scirrhous GC, and Borrmann type 4 AGC. To distinguish each of these cancers, knowledge of their endoscopic and pathological differences is necessary, especially for LP type GCs in the developmental stage. In conclusion, diagnosis of pre-stage or latent LP type GC before progression to typical LP type GC requires the detection of IIc-like lesions in the fundic gland area. It is also crucial to identify any abnormalities such as sclerosis of the gastric wall and hypertrophy of the mucosal folds during endoscopy.

Determination of the optimal cutoff percentage of residual tumors to define the pathologic response rate (pathRR) of gastric cancer (GC) treated with preoperative therapy (JCOG1004-A).

4104 Background: PathRR is a common endpoint used to assess the efficacy of preoperative therapy for GC. PathRR is estimated based on the percentage of the residual tumor area in the preexisting tumor bed. Various cut-off definitions that have used for past studies (e.g. 10%, 33%, 40%, 50%, 67%) often impair the comparability of pathRRs between studies. Methods: Individual patient data from four JCOG trials evaluating preoperative chemotherapy were used (JCOG0001, irinotecan+cisplatin, n=55; JCOG0002, S-1, n=55; JCOG0210, S-1+cisplatin, n=50; JCOG0405, S-1+cisplatin, n=53). Pathological specimens were evaluated from 173 out of 188 patients (92%) who underwent surgery. Residual and preexisting tumor areas were traced on a virtual microscopic slide by one pathologist and another confirmed these areas. The hazard ratio (HR) in overall survival was calculated for each cut-off percentage by stratified Cox regression analysis including the study as a stratification factor, and concordance probability estimates (CPE) were also calculated. Results: The numbers of patients with 0-10%/11-33%/34-50%/51-66%/67-100% residual tumors were 43/33/27/23/47, respectively. Overall, HR was the largest in the 10% cut-off and CPE was the largest in 33%. When patients with R1/R2 resections were excluded, both HR and CPE were the largest in the 10% cut-off. In subgroup analyses, almost all cut-offs predicted survival well regardless of the histologic type (intestinal/diffuse), and no cut-off predicted survival for type 4 (linitis plastica type) tumors. Conclusions: PathRR is not recommended for clinical trials including type 4 tumors. The 10% cut-off is recommended for non-type 4 tumors, though 33% is also applicable. [Table: see text]

胃癌術後8年目に再発したlinitis plastica型大腸転移の1例

胃癌術後8年目に再発したlinitis plastica型大腸転移の1例

A Case of Mantle Cell Lymphoma Exhibiting Features of Gastric Linitis Plastica Type of Advanced Gastric Cancer

Mantle cell lymphoma has a broad spectrum of endoscopic presentations, such as thick, rigid folds that are indispensible on air insufflation, superficial confluent ulceration, or a polypoidal mass protruding into the lumen. The exact diagnosis is difficult to make because the lesion is in the submucosal layer and inaccessible by biopsy. Lesions will often exfoliate necrotic cells which make interpretation difficult, or they may be too small in number and size and thus indistinguishable from anaplastic carcinoma. We report a case of mantle cell lymphoma with diffuse wall thickening of the whole stomach in a 51-year-old man. The series of endoscopic findings in this case support the role of differential diagnosis of linitis plasica type of advanced gastric cancer with mantle cell lymphoma. (Korean J Helicobacter Up Gastrointest Res 2012;12:42-46)

A phase II study of preoperative chemotherapy with S-1 (S) and cisplatin (P) followed by D3 gastrectomy for gastric cancer (GC) with extensive lymph node metastasis (ELM): Survival results of JCOG0405.

70 Background: GC with ELM, especially in case of M1(LYM), is regarded unresectable in many countries, while challenge is ongoing in Japan to treat them by intensive chemotherapy followed by super extended surgery. In our previous phase II study (JCOG0001) for the same population, iritotecan plus P (IP) chemotherapy followed by surgery showed remarkable survival of 27.0% at 3 years but its toxicity led to rather high treatment related death (TRD). Development of safer and more effective treatment is urged. Methods: Eligibility criteria included histologically proven gastric adenocarcinoma; bulky nodal involvement around major branched arteries to the stomach and/or para-aortic nodal metastases; cM0 (except para-aortic nodes); negative lavage cytology; not linitis plastica type; PS of 0 or 1. Patients (pts) received two or three 28- day cycles of induction chemotherapy of S (80 mg/m2 from day 1 to 21) and P (60 mg/m2 on day 8), and then underwent D3 gastrectomy. Primary endpoint was R0 resection and key secondary endpoint was 3-year survival. Other secondary endpoints included response rate and adverse events. Results: Between 02/2005 and 06/2007, 53 pts were enrolled and 2 pts were ineligible. Only surrogate endpoints of efficacy and feasibility were reported in ASCO-GI 2008, which included clinical response of 64.7%, R0 of 82.4%, pathological response of 51.0%, and no TRD with low toxicities. The 3-year overall survival, which we first clarified in this report, was 58.8% (95% CI, 44.1-70.9%). Conclusions: Preoperative SP followed by D3 gastrectomy demonstrated excellent 3-year survival with low mortality compared with preoperative IP, which was far better result than expected against this unresectable population. This multimodal treatment is highly promising for GC with ELM. [Table: see text]

An integrated analysis of two phase II trials (JCOG0001 and JCOG0405) of preoperative chemotherapy followed by D3 gastrectomy for gastric cancer (GC) with extensive lymph node metastasis (ELM).

90 Background: GC with ELM (bulky N2 metastasis and / or para-aortic lymph node metastases [PAN]) is commonly regarded unresectable, while in JCOG combined modality treatment has been tested since 2000 (JCOG0001 and JCOG0405). Both trials met their primary endpoints (i.e., 3 year-survival of 27.3% in JCOG0001 and R0 resection of 82.4% in JCOG0405). The survival and the toxicity profile were quite different between the trials despite the similar eligibility with an outstanding 3-year survival of 58.8% in JCOG0405. This study is conducted to explore if survival is still better in JCOG0405 after adjusting baseline factors and if there is a subset of patients (pts) who benefit more from either treatment. Methods: Eligibility criteria for both included histologically proven gastric adenocarcinoma; bulky nodal involvement around major branched arteries to the stomach and/or PAN; cM0 (except PAN); negative lavage cytology; not linitis plastica type; PS of 0 or 1. Pts received two or three cycles of induction chemotherapy of IP: irinotecan (70 mg/m2 on day 1 and day 15) and cisplatin (80 mg/m2 on day 1) in JCOG0001, or SP: S1 (80 mg/m2 from day 1 to 21) and cisplatin (60 mg/m2 on day 8) in JCOG0405, followed by D3 gastrectomy. Multivariate analysis for overall survival adjusting baseline factors and treatment (IP/SP) was performed with a Cox regression model. Interaction tests were also carried out between baseline factors and treatment. Results: After adjusting baseline factors, SP was superior than IP for overall survival (HR=0.335: 0.184 – 0.612). There was only interaction effect between treatment and the status of lymph node metastases (bulkyN+/PAN- vs bulkyN-/PAN+ vs bulkyN+/PAN+; p=0.1306). Conclusions: SP was shown to be the favorable treatment for GC with ELM by multivariate analysis, while poor prognosis in pts having both bulky N+ and PAN+ may necessitate further treatment improvement. No significant financial relationships to disclose.

A phase II study of preoperative chemotherapy (CX) with S-1 and cisplatin followed by gastrectomy for clinically resectable type 4 and large type 3 gastric cancer: JCOG 0210

4609 Background: Prognosis of both linitis plastica (type 4) and large ulcero-invasive type (type 3) gastric cancer is poor even after curative resection. We conducted a phase II study to evaluate the safety and efficacy of preoperative CX with S-1 and cisplatin followed by gastrectomy in patients (pts) with these tumors. Methods: Eligibility criteria included histologically proven adenocarcinoma of the stomach; clinically resectable gastric cancer of type 4 or type 3 of =8 cm; cN0–2; cM0; PS 0–1; 20–75 years old. Pts received two 28-day cycles of induction CX of S-1 (80–120 mg/body, po, day 1–21) and cisplatin (60mg/m2, iv, day 8). Gastrectomy with D2/3 dissection was performed within 3 to 5 weeks after CX. No adjuvant therapy was added until recurrence after the curative gastrectomy. Primary endpoints were the proportion of protocol achievement and incidence of treatment related death (TRD). Sample size was determined to reject the rate of 45% under the expectation of 60% with power of 80% and alpha of 10%. Results: Fifty pts, 29 males and 21 females with a median age of 61 years (range: 32–75), were entered in this study between 03/2003 and 12/2003. Type 3/4 ratio was 20/30. Surgical exploration was carried out in 48 pts (96%). Among 49 eligible pts, 36 pts (73%; 95% CI, 59–85%) received two cycles of induction CX and R0 resection. One TRD was observed during the first course of CX due to uncontrollable hemorrhage from the primary tumor. Median survival time and the 3- year OS were 1.44 years (95% CI, 1.26–1.98) and 26.0% (95% CI, 14.9–38.6%), respectively. Pathological response, defined as disappearance of more than one third of the primary tumor, was confirmed in 24 pts (48%) and pathological complete response was seen in 1 pts (2%). During the CX, grade 3/4 neutropenia and anorexia occurred in 7 pts (14%), respectively. Postoperative morbidity included pneumonia in 2 pts, pancreatic leakage in 4, and intraperitoneal abscess in 3, without any mortality. Conclusions: Preoperative CX with S-1 and cisplatin followed by gastrectomy was safe and promising for type 4 and large type 3 gastric cancer. The results of ongoing phase III study to evaluate this treatment are awaited. No significant financial relationships to disclose.

Pathology and prognosis of carcinoma of the stomach.

Abstract The pathology and prognosis of 205 patients treated by total or partial gastrectomy for carcinoma of the stomach during the years 1951-5 have been evaluated. One hundred and sixteen patients (61 per cent) had a partial gastrectomy and 74 (39 per cent) had a total gastrectomy. The overall postoperative mortality was 25 per cent and this was greater for total than for partial gastrectomy. The crude survival rate was 19.4 per cent at 5 years and 11.4 per cent at 10 years. Carcinoma of the cardia had a worse prognosis than tumours at other sites. There were no 5-year survivors among patients with the linitis plastica type of carcinoma of the stomach. Tumours classified as poorly differentiated or anaplastic carcinoma had a poorer prognosis than well-differentiated adenocarcinomas. The amount of lymphocytic and plasma-cell infiltration of the tumour has a very significant effect on prognosis. Five out of the 7 patients with a heavy infiltrate of such cells survived over 5 years. Lymph-node involvement is the feature having the greatest influence on prognosis. There was a 40 per cent 5-year survival rate in the absence of node involvement and an 11 per cent 5-year survival rate with involved nodes. Patients with involved nodes surviving over 5 years had, on the average, fewer positive glands than those with involved nodes who survived for less than 5 years. No benefit follows from total rather than partial gastrectomy provided the cancer and regional lymph-nodes can be removed with the simpler procedure. Four case reports are presented to illustrate the difficulties in assessing the prognosis of gastric cancer.

Novel models for human scirrhous gastric carcinoma in vivo

Human scirrhous gastric carcinoma, a diffusely infiltrating type of poorly differentiated gastric carcinoma also known as linitis plastica type carcinoma, is characterized by cancer cell infiltration and proliferation accompanied with extensive stromal fibrosis. We established two new gastric cancer cell lines, designated OUCM-8 and OCUM-11, which developed the characteristic biology of scirrhous gastric carcinoma upon orthotopic implantation in mice. Involvement of lymph nodes and liver metastasis was also found in both orthotopic models. Histologically, these orthotopic models showed proliferation with extensive fibrosis, resembling human scirrhous gastric cancer. Both cell lines were derived from ascites of patients with scirrhous gastric cancer. The growth of OCUM-8 and OCUM-11 cells following the addition of KGF, FGF, and EGF was increased significantly relative to untreated cells. An increase in the number of attached and spreading cells occurred following the addition of TGF-beta 1 in both cell lines. OCUM-11 cells showed microsatellite instability. Although subcutaneous scirrhous gastric cancer cells show medullary growth, most in vivo studies of scirrhous gastric cancer have used xenografted tumors implanted subcutaneously. Only in a few cases was it confirmed that these scirrhous gastric cancer cell lines retained the original histologic characteristics. Our orthotopic models should contribute to the elucidation of disease progression in situ and to the development of therapy for scirrhous gastric cancer.

Detection of disseminated cancer cells in linitis plastica-type gastric carcinoma.

Dissemination of cancer cells in the abdominal cavity may lead to peritoneal carcinomatosis, a common event in the linitis plastica type of gastric carcinoma. Reverse transcriptase polymerase chain reaction (RT-PCR) is a sensitive technique for detecting these cells. Peritoneal washings were obtained during laparotomy from 47 consecutive linitis plastica patients who preoperatively were considered candidates for curative resection. Together with conventional cytological examination using Papanicolaou staining, real-time RT-PCR was performed to quantitate prospectively carcinoembryonic antigen (CEA) mRNA in these washings. Samples above a cutoff value for CEA mRNA were considered positive for molecular detection of disseminated cancer cells. Conventional cytological examination was positive in 43% (20/47). Positivity of CEA mRNA was much higher at 83% (39/47) and peritoneal carcinomatosis actually was observed in 77% (36/47), either at laparotomy or during postoperative follow-up. Although only two of eight patients who were negative for CEA mRNA suffered from peritoneal carcinomatosis, three more patients died of recurrences through other metastatic pathways. Multivariate analysis revealed that curability of the operation (knowledge of the CEA mRNA values excluded) and T categories were the only significant independent prognostic factors. RT-PCR of the peritoneal washes had little value as a prognostic factor, but identified over 80% of the patients planned for curative surgery to have disseminated cancer cells in the peritoneal cavity. Almost the same proportion of patients actually suffered from peritoneal carcinomatosis. These facts indicate why treatment with surgery alone rarely cures patients with linitis plastica.

Radiological spectrum of late sequelae of corrosive injury to upper gastrointestinal tract. A pictorial review.

To evaluate the radiological spectrum of sequelae of corrosive acid and alkali injury to the upper gastrointestinal (GI) tract using barium contrast examination. Barium contrast radiographic films of 155 patients with a history of corrosive ingestion, acid in 120 and alkali in 35 patients with grade 2b and 3 injury on initial endoscopy, were retrospectively evaluated. Barium contrast examination of the upper GI tract was performed in the course of follow-up, beyond 3 weeks of corrosive ingestion. The esophagus was involved in 131 patients and the stomach in 74. Fifty patients had simultaneous involvement of esophagus and stomach. Radiological findings in the esophagus were solitary or multiple strictures of varying length, intramural pseudodiverticula, and carcinoma in long-standing corrosive injury. The stomach showed cicatrization, predominantly involving the antrum, linitis plastica type deformity with multiple pseudodiverticula. There was no difference in the radiological findings as to the type of corrosive ingested. Barium examination of the upper GI tract is useful in the evaluation of late sequelae of corrosive injury (acid/alkali). There was no difference in the radiological findings as to the type of corrosive ingested. Thus, contrary to general belief, we found that acid and alkali damage both the esophagus and the stomach with equal degree of severity.

Intestinal epithelial lesions associated with signet ring cell carcinoma of the colon and small intestine

The purpose of this study was to investigate the epithelial lesions associated with signet ring cell carcinoma (SRCC) of the colon and small intestine and the possible mechanism of tumour development. Twenty-seven cases of adenocarcinoma with a signet ring cell (SRC) component of the colon and small intestine were divided into three groups depending on the association of the SRCC with: (1) epithelium without definite epithelial dysplasia, (2) adenoma, and (3) common type of adenocarcinoma (CTCA) with SRCC component occupying more than 50%, 30%, or less than 30% of the tumour. Most carcinomas were of T3 or T4 type, using the TNM standard staging system. The SRCC component was histopathologically similar in all groups. In group 1 (four cases, linitis plastica type), the overlying epithelium was normal or showed indefinite epithelial dysplasia and occasionally contained intra-epithelial SRCs. In groups 2 and 3 (two and 21 cases, respectively), seven cases contained multiple foci of intra-epithelial SRCs in areas separated from the invasive carcinoma. Transitional areas between SRCC and adenoma or CTCA were also identified. Immunostaining for p53 showed a varied extent of positive reactivity in 23 SRCC. The degree and the extent of reactivity appeared to increase with the stage of the carcinoma. Most intra-epithelial SRCs were immunoreactive for p53. Linitis plastica SRCC was associated with extensive p53 reactivity of the 'atypical' and the adjacent 'normal' epithelium. SRCC may arise from either CTCA, adenoma, 'atypical' epithelium or a combination of these epithelia. SRCC accounts for the bulk of carcinoma in each of these categories. In linitis plastica SRCC, positive reactivity for p53 is extensive in the adjacent 'normal' colonic epithelium and extends as far as 3cm from the microscopically identified SRCC margin.

CLINICAL CHARACTERISTICS and PROGNOSIS OF COLORECTAL SIGNET‐RING CELL CARCINOMA

Background/aims Colorectal signet‐ring cell carcinoma (SRCC) is uncommon tumor. The aim of this study was to evaluate the clinical characteristics of primary and metastatic colorectal SRCC.Methods We retrospectively examined the records of patients who had undergone surgery for colon cancer and was diagnosed pathologically as colorectal SRCC from 1988 to 2000.Results Among 1812 patients with colorectal cancer examined, the number of patients with SRCC was 28 (1.5%); eight patients (28.6%) were metastatic and 20 patients (71.4%) were primary. Male to female ratio was 19:9 and mean age was 44.2 (primary, 42.5; metastatic, 48.3). Mean age of primary SRCC of rectosigmoid area was lower than that of ascending colon (37.4 vs. 54.5). The topographic incidences of primary SRCC were nine patients in rectum; five patients in sigmoid colon; six patients in ascending colon. Metastatic SRCC's were mostly found in splenic flexure and rectosigmoid area. Biopsy positive rate at first was 13 of 18 in primary SRCC, and 3 of 5 in metastatic SRCC. Five cases (55.6%) of primary rectal SRCC showed linitis plastica type. The stage of primary SRCC showed a preponderance of Astler–Coller C2 lesions; 3 (15%) were in B2, 1 (5%) was in C1, 14 (70%) were in C2, 2 (10%) were in D. One and two years survival of primary SRCC were 62.7 and 45.7%, respectively.Conclusions Colorectal SRCC is rare among colon cancer and common in young age group especially which is primary or occurs in rectosigmoid area. The primary SRCC's were mostly found in advanced stage, and the prognosis might be poor.

Intestinal metastases from gastric adenocarcinoma: helical CT findings.

The purpose of this work was to describe the helical CT findings of intestinal metastasis from gastric adenocarcinoma. Twenty-three patients with intestinal metastasis from gastric adenocarcinoma found at helical CT were included. CT findings and clinical and pathologic data were reviewed. The most common characteristic finding was target-like concentric bowel wall thickening (thick inner high-outer low, n = 18) involving multiple long segments with progressive thickening of the enhancing inner layer. Fifteen cases (65%) involved multiple sites, and the ascending colon (n = 12) and rectum (n = 11) were the two most common sites. Peritoneal carcinomatosis (n = 15, 65%) and bowel obstruction (n = 14, 61%) were common associated findings. Regarding the primary lesion, the majority was linitis plastica (n = 16) and poorly differentiated adenocarcinoma with or without signet-ring cell differentiation (n = 14). Intestinal metastasis from gastric adenocarcinoma, especially of the linitis plastica type, most commonly showed target-like long segmental wall thickening with a characteristically thick inner enhancing layer on helical CT.