Prognostic impact and survival outcomes of colon perforation in patients with metastatic colorectal cancer: a multicenter retrospective cohort study.

BACKGROUND: Colon perforation caused by colorectal cancer (CRC) is a fatal condition requiring emergency intervention. For patients with metastatic lesions, surgeons face difficult decisions regarding whether to resect the primary and metastatic lesions. Moreover, there is currently no established treatment strategy for these patients. This study aimed to investigate the clinical practice and long-term outcomes of patients with metastatic CRC diagnosed with the onset of colon perforation. METHODS: We performed a population-based multicenter cohort study. Consecutive patients diagnosed with stage IV CRC between 2008 and 2015 at all designated cancer hospitals in Fukushima Prefecture, Japan, were enrolled in this study. We evaluated the impact of colon perforation on the survival outcomes of patients with metastatic CRC. The main outcome was the adjusted hazard ratio (aHR) of perforation for overall survival (OS). Survival time and HRs were estimated using Kaplan‒Meier and Cox proportional regression analyses. RESULTS: A total of 1258 patients were enrolled (perforation: n = 46; non-perforation: n = 1212). All but one of the patients with perforation underwent primary resection or colostomy and 25 cases were able to receive chemotherapy. The median OS for the perforation and non-perforation groups was 19.0 and 20.0 months, respectively (p = 0.96). Moreover, perforation was not an independent prognostic factor (aHR: 0.99; 95% confidence interval: 0.61-1.28). CONCLUSIONS: In metastatic CRC, perforation is not necessarily a poor prognostic factor. Patients with perforation who undergo primary tumor resection or colostomy and prompt initiation of systemic chemotherapy might be expected to have a survival time similar to that of patients with non-perforated colon.

Simultaneous and sequential combination of genetic and epigenetic biomarkers for the presence of high-grade dysplasia in patients with pancreatic cyst: Discovery in cyst fluid and test in pancreatic juice.

BACKGROUND/OBJECTIVES: Screening patients with intraductal papillary mucinous neoplasms (IPMN) has the primary goal of identifying potentially curable noninvasive precursors. We aimed to evaluate the diagnostic impact of genetic and epigenetic biomarkers in the presence of noninvasive precursors. METHODS: Mutated KRAS/GNAS and methylated SOX17/TBX15/BMP3/TFPI2 DNA were assessed by droplet digital PCR in a discovery cohort of 70 surgically aspirated cyst fluids, and diagnostic performances for differentiating high-grade dysplasia (HGD) from low-grade dysplasia (LGD) was evaluated. We then tested these markers using an independent test cohort consisting of 156 serially collected pancreatic juice samples from 30 patients with IPMN. RESULTS: Mutated KRAS and GNAS are specific for IPMNs but are not helpful for the prediction of histological grades. Cyst fluids from IPMN with HGD showed higher methylation levels of SOX17 (median, 0.141 vs. 0.021; P = 0.086) and TBX15 (median, 0.030 vs. 0.003; P = 0.028) than those with LGD. The combination of all tested markers yielded a diagnostic performance with sensitivity of 69.6%, and specificity of 90.0%. Among the 30 pancreatic juice samples exhibiting the highest abundance of KRAS/GNAS mutations in each patient in the test cohort, patients with histologically proven HGD due to pancreatic resection had a significantly higher prevalence (100% vs. 31%, P = 0.018) and abundance (P = 0.037) of methylated TBX15 than those without cytohistological diagnosis undergoing surveillance. CONCLUSIONS: A simultaneous and sequential combination of mutated and methylated DNA markers in pancreatic cyst fluid and juice sample markers can help detect noninvasive pancreatic precursor neoplasms.

Clinical Features and Survival of Young Adults with Stage IV Gastric Cancer: a Japanese Population-Based Study.

PURPOSE: With the aging of society, the mean age of patients with gastric cancer (GC) in Japan has increased. However, there are few documented outcomes for young patients with stage IV GC. We investigated the clinical characteristics and prognosis of such patients aged < 40 years using a dataset from an integrated population-based cohort study. METHODS: We conducted this multicenter population-based cohort study to determine whether earlier onset of GC was a poor prognostic factor. We enrolled patients with metastatic GC aged < 40 years (young group) and those aged between 60 and 75 years (middle-aged group). Patients were histologically diagnosed as having gastric adenocarcinoma. We evaluated the overall survival (OS) of both groups and the hazard ratio (HR) for OS based on age. The adjusted HR with 95% confidence interval (CI) was evaluated using the Cox proportional hazards model after adjusting for confounding factors, including sex, histology, number of metastatic lesions, surgical resection, and chemotherapy. RESULTS: This study enrolled 555 patients. The patients were classified into the young (n = 20) and the middle-aged group (n = 535). The median OS durations were 5.7 and 8.8 months in the young and middle-aged groups, respectively (p = 0.029). The adjusted HR (95% CI) of the young group was 1.88 (1.17-3.04, p = 0.009). CONCLUSION: Age was an independent prognostic factor in patients with stage IV GC. Further studies investigating the genomic characteristics of GC and exploring more effective chemotherapeutic agents are required.

Impact of histological subtype on prognosis in stage IV colorectal cancer: A population-based cohort study.

BACKGROUND: There are a few established prognostic factors for stage IV colorectal cancer. Thus, this study aimed to evaluate the impact of histological subtypes on prognosis and metastatic patterns in patients with stage IV colorectal cancer. METHODS: This was a population-based, multicenter, cohort study. We included consecutive patients diagnosed with stage IV colorectal cancer between 2008 and 2015 at all designated cancer hospitals in Fukushima prefecture, Japan. Patients were classified into two groups according to histological subtypes as follows: poorly differentiated adenocarcinoma (Por), mucinous adenocarcinoma (Muc), or signet-ring cell carcinoma (Sig) and well (Wel) or moderately differentiated adenocarcinoma (Mod). We evaluated the relationship between these histological groups and survival time. After adjusting for other clinical factors, we calculated the hazard ratio for Por/Muc/Sig. RESULTS: A total of 1,151 patients were enrolled, and 1,031 and 120 had Wel/Mod and Por/Muc/Sig, respectively. The median overall survival was 19.2 and 11.9 months for Wel/Mod and Por/Muc/Sig, respectively (p < 0.001). The adjusted hazard ratio for Por/Muc/Sig with regard to survival time was 1.42 (95% confidence interval: 1.13-1.77). Por/Muc/Sig had a lower incidence of liver and lung metastases and a higher incidence of peritoneal dissemination and metastasis to rare organs, such as the bone and brain. CONCLUSIONS: The Por/Muc/Sig histological subtype was an independent prognostic factor for poor prognosis among patients with stage IV colorectal cancer. The histological subtype may be useful for predicting the prognosis of patients with stage IV colorectal cancer and designing the treatment strategy.

Clinical impact of gastrectomy for gastric cancer patients with positive lavage cytology without gross peritoneal dissemination.

BACKGROUND: The prognosis of gastric cancer patients with positive lavage cytology without gross peritoneal dissemination (P0CY1) is poor. The survival benefit of gastrectomy for these patients has not been established. PATIENTS AND METHODS: In this population-based cohort study, we investigated the impact of radical gastrectomy with lymph node dissection for P0CY1 patients. Patients who were diagnosed with Stage IV gastric cancer from 2008 to 2015 in all nine cancer-designated hospitals in a tertiary medical area were listed. Patients who were diagnosed with histologically proven adenocarcinoma in both the primary lesion and lavage cytology during the operation or a diagnostic laparoscopic examination were enrolled. Patients with a gross peritoneal lesion or other metastatic lesions were excluded. The primary outcome was the adjusted hazard ratio (aHR) of gastrectomy for overall survival. We also evaluated the survival time in patients who underwent gastrectomy or chemotherapy in comparison to patients managed without primary surgery or with best supportive care. RESULTS: One hundred patients were enrolled. The aHR (95% confidence interval) of gastrectomy was 0.677 (0.411-1.114, p = 0.125). The median survival time in patients who received gastrectomy (n = 74) was 21.7, while that in patients managed without primary surgery (n = 30) was 20.5 months (p = 0.155). The median survival time in patients who received chemotherapy (n = 76) was 23.0 months, while that in patients managed without chemotherapy was 8.6 months (p < 0.001). CONCLUSION: Gastrectomy was not effective for improving the survival time in patients with P0CY1 gastric cancer. Surgeons should prioritize the performance of chemotherapy over surgery as the initial treatment.

Clinical Impact of Primary Tumor Site in Stage IV Colorectal Cancer: A Statewide Cohort Study.

BACKGROUND/AIM: We investigated the clinical impact of the primary tumor site in stage IV colorectal cancer (CRC). PATIENTS AND METHODS: In this statewide multicenter retrospective cohort, patients with stage IV CRC from nine hospital-based cancer registries across the Fukushima Prefecture (2008-2015) were categorized based on three primary tumor sites: right colon cancer (RCC), left colon cancer (LCC), and rectal cancer. Overall survival was assessed using Cox regression analysis. RESULTS: A total of 1,211 patients were included. The most common clinical symptom was obstruction in LCC and bleeding in rectal cancer. Liver metastases were multiple and larger in LCC, while lung metastases were multiple in rectal cancer. Compared to LCC, the adjusted hazard ratio (HR) for overall survival was 1.19 [95% confidence interval (CI)=1.01-1.39, p=0.032] in RCC and 1.03 (95% CI=0.86-1.23, p=0.77) in rectal cancer. CONCLUSION: RCC was independently associated with a worse prognosis in stage IV CRC.

A grading system for predicting the prognosis of gastric cancer with liver metastasis.

OBJECTIVE: The prognosis of patients with liver metastases from gastric cancer is determined using tumor size and number of metastases; this is similar to the factors used for the prediction of liver metastases from colorectal cancer. The relationship between the degree of liver metastasis from gastric cancer and prognosis with reference to the classification of liver metastasis from colorectal cancer was investigated. METHODS: This was a multi-institutional historical cohort study. Among patients with stage IV gastric cancer, who visited the cancer hospitals in Fukushima Prefecture, Japan, between 2008 and 2015, those with simultaneous liver metastasis were included. Abdominal pretreatment computed tomography images were reviewed and classified into H1 (four or less liver metastases with a maximum diameter of ≤5 cm); H2 (other than H1 and H3) or H3 (five or more liver metastases with a maximum diameter of ≥5 cm). The hazard ratio for overall survival according to the H grade (H1, H2 and H3) was calculated using the Cox proportional hazards model. RESULTS: A total of 412 patients were analyzed. Patients with H1, H2 and H3 grades were 118, 162 and 141, respectively, and their median survival time was 10.2, 5.7 and 3.1 months, respectively (log-rank P < 0.001). The adjusted hazard ratio for overall survival was H1: H2: H3 = reference: 1.39 (95% confidence interval: 1.04-1.85): 1.69 (95% confidence interval: 1.27-2.27). CONCLUSIONS: The grading system proposed in this study was a simple and easy-to-use prognosis prediction index for patients with liver metastasis from gastric cancer.

Benefit of intensive chemotherapy for elderly patients aged 80 years or older with metastatic colorectal cancer: a state-wide multicenter cohort study.

BACKGROUND: It remains unclear whether intensive chemotherapy for Stage IV colorectal cancer (CRC) patients aged 80 years or older is beneficial prognostically. This study aimed to investigate the overall survival of Stage IV CRC patients aged ≥ 80 years receiving intensive chemotherapy. METHODS: The study design was a population-based, multicenter, historical cohort study. The extracted participants' data were consecutive patients diagnosed as Stage IV CRC between January 2008 and May 2015 in nine hospitals in Japan. Patients were classified into two groups according to age: aged group (≥ 80 years) and younger group (< 80 years old). Intensive chemotherapy was defined as at least two courses of doublet chemotherapy with oxaliplatin-or irinotecan-based regimens. The primary outcome was the adjusted hazard ratio (HR) of age ≥ 80 years in patients who undergoing intensive chemotherapy. RESULTS: During the study period, 1259 patients were treated for Stage IV CRC in the participating hospitals. In total, 231 patients (18.3%) were in the aged group, and 1028 (81.7%) were in the younger group, and 788 (62.6%) underwent intensive chemotherapy. The median overall survival for the aged and younger group patients was 21.0 months (interquartile range (IQR), 10.6-34.1 months) and 24.3 months (IQR 12.6-39.3 months), respectively. The adjusted HR of age ≥ 80 years was 1.29 (confidence intervals 0.84-2.00). CONCLUSION: Stage IV CRC patients aged 80 years or older receiving intensive chemotherapy had a similar prognosis to those aged < 80 years. Avoiding intensive chemotherapy for mCRC patients simply because they are ≥ 80 years old is not recommended.

Small bowel GIST with hemorrhagic shock diagnosed by capsule endoscopy and double-balloon endoscopy, angiography-guided hemostasis, and laparoscopic-assisted resection.

Small bowel tumors presenting with hemorrhagic shock require urgent treatment with angiographic embolization to achieve hemostasis. Capsule endoscopy and double-balloon endoscopy are useful for localizing the tumor, diagnosis, and guiding surgery.

An ascites grading system for predicting the prognosis of gastric cancer with peritoneum dissemination.

AIM: Gastric cancer with peritoneum dissemination is intractable with surgical resection. The evaluation of the degree of dissemination using computed tomography (CT) is difficult. We focused on the amount of ascites based on CT findings and established a scaling system to predict these patients' prognoses. METHODS: We extracted individual data from a population-based cohort. Patients diagnosed with histologically proven gastric adenocarcinoma with peritoneum dissemination were enrolled. Two raters evaluated the CT images and determined the grade of ascites in each patient: grade 0 indicated no ascites in all slices; grade 1 indicated ascites detected only in the upper or lower abdominal cavity; grade 2 indicated ascites detected in both the upper and lower abdominal cavities; and grade 3 indicated ascites extending continuously from the pelvic cavity to the upper abdominal cavity. We evaluated the relationship between the ascites grade and survival time. After adjusting for other clinical factors, we calculated hazard ratios of each ascites grade. RESULTS: A total of 718 patients were enrolled. The number of patients with grades 0, 1, 2, and 3 were 303, 223, 94, and 98, respectively. The median overall survival times were 16.0, 8.7, 5.4, and 3.0 months for ascites on CT grades 0, 1, 2, and 3, respectively (P < .001). The adjusted hazard ratios for the survival time were 1.74 (1.33-2.26, P < .001), 3.20 (2.25-4.57, P < .001), and 4.76 (3.16-7.17, P < .001) for grades 1, 2, and 3, respectively. CONCLUSION: We established a new grading system of pretreatment ascites to better predict the prognosis of gastric cancer.

Pancreaticoduodenectomy following total occlusion of the superior mesenteric artery: a case report and literature review.

BACKGROUND: Patients with chronic occlusion of the celiac artery and superior mesenteric artery (SMA) are often asymptomatic, and occlusion may be caused by arteriosclerosis or median arcuate ligament compression. Pancreaticoduodenectomy (PD) is occasionally performed for patients with celiac artery occlusion; however, reports on patients with SMA occlusion are rare. We report a patient with cholangiocarcinoma and total atherosclerotic occlusion of the SMA without preoperative stenting or bypass. CASE PRESENTATION: A 73-year-old man suspected to have lower bile duct carcinoma was admitted to our hospital for further treatment. Three-dimensional computed tomography (3DCT) showed a common bile duct tumor and total occlusion of the SMA with collateral circulation of the gastroduodenal artery (GDA) and inferior mesenteric artery (IMA). We performed a PD. During the operation, we used test clamping of the GDA, which revealed no bowel ischemia. The postoperative course was uneventful, and the patient was discharged on postoperative day (POD) 30. 3DCT on POD 98 and POD 307 showed development of collateral circulation between the IMA and SMA. CONCLUSION: Here, we report the case of a patient with total occlusion of the SMA who subsequently underwent PD. 3DCT was instrumental in gathering vascular collateral information and thus we conclude that the assessment of collateral circulation before surgery is important.

Clinical features of isolated proximal-type immunoglobulin G4-related sclerosing cholangitis.

BACKGROUND AND AIM: Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) presents as isolated proximal-type sclerosing cholangitis (i-SC). The present study sought to clarify the imaging differences between i-SC and Klatskin tumor. Differences between i-SC and IgG4-SC associated with autoimmune pancreatitis (AIP-SC) were also studied. METHODS: Differentiating factors between i-SC and Klatskin tumor were studied. Serum IgG4 level, CA19-9 level, computed tomography (CT) findings, cholangiography findings (symmetrical smooth long stricture extending into the upper bile duct [SSLS]), endosonographic features (continuous symmetrical mucosal lesion to the hilar part [CSML]), endoscopic biopsy results, treatment, relapse, and survival were also compared between patients with i-SC and those with AIP-SC. RESULTS: For a differential diagnosis between i-SC (N = 9) and Klatskin tumor (N = 47), the cut-off value of serum IgG4 level was 150 mg/dL (sensitivity, 0.857, specificity, 0.966). Logistic regression analysis indicated that serum IgG4 level, presence of SSLS, presence of CSML, and presence of swollen ampulla are independent factor for identifying i-SC. Relapse rate was significantly higher in the IgG4-SC with AIP group than in the i-SC group (log rank, P = 0.046). CONCLUSION: Isolated proximal-type sclerosing cholangitis presents as a nodular lesion with SSLS and/or CSML mimicking a Klatskin tumor. Those endoscopic features might provide a diagnostic clue for i-SC. i-SC is likely to have a more favorable prognosis than IgG4-SC with AIP.

Massive retroperitoneal hematoma following colonoscopy: A case report.

RATIONALE: Colonoscopy has been used for screening and treatment of diseases worldwide. Endoscopic mucosal resection (EMR) has many major complications such as colon perforation and bleeding. However, cases of minor complications have also been reported. Here, we present a case of massive retroperitoneal hematoma, as a minor complication, after colonoscopy. PATIENT CONCERNS: A 57-year-old man was admitted to our hospital because of abdominal pain. He had no past medical history relating to his present condition, and he received EMR at another hospital 11 days before his admission. Dynamic computed tomography (CT) was performed, which showed a massive retroperitoneal hematoma near the third portion of the duodenum. DIAGNOSIS: The patient had a superior mesenteric vein injury after the colonoscopy. OUTCOMES: The patient did not complain of nausea or vomiting and was discharged after 43 days. LESSONS: Although massive retroperitoneal hematoma is a minor complication after colonoscopy, it can be life threatening; thus, we need to know more about this complication. Dynamic CT may be useful in detecting whether the bleeding occurs from the artery or not.

Intraductal papillary neoplasm arising from peribiliary glands connecting with the inferior branch of the bile duct of the anterior segment of the liver.

Intraductal papillary neoplasms of the bile duct are generally thought to arise from neoplastic papillary proliferation of epithelial cells lining the bile duct. We herein report a case with findings that strongly suggested that the biliary cystic tumor might have derived from a peribiliary gland. A 69-year-old female was found to have a cystic lesion with intracystic protrusions at the anterior segment of the right hepatic lobe and underwent hepatic anterior segment resection. Fluoroscopy of the resected specimen injected with contrast medium into the cyst revealed a connection between the cystic lesion and the bile ducts. The cyst was multilocular in appearance. On microscopic examination, the cyst was located within the portal tract of the inferior branch of the anterior segment and connected with the inferior branch of the bile duct. The wall of the hepatic cyst lacked an ovarian-like stroma. The tumor was composed of papillary and glandular components, and the tumor cells were similar to gastric foveolar and pyloric gland epithelia and regarded as adenoma. These tumor cells were positive for MUC 5AC, MUC6, and HIK1083. The tumor was finally diagnosed as an intraductal papillary neoplasm of the bile duct (adenoma, gastric type) arising from a peribiliary gland.

[Case of gallbladder cancer in which the surface structure of gallbladder was clarified using the endoscopic double contrast cholecystography].

A 75-year-old woman was admitted to our hospital with a gallbladder tumor by detected ultrasonography (US). On endoscopic ultrasonography (EUS), and abdominal CT, we diagnosed the Is+IIa+IIb-like ss lesion invasive gallbladder cancer, but endoscopic double contrast cholecystography suggested IIa+IIb-like ss invasive gallbladder cancer because the lesion had the same granular membrane a other cancer membrane and cholecystectomy was carried out. The pathologic diagnosis was IIa+IIb-like ss invasive gallbladder cancer.

Experimental trial for diagnosis of pancreatic ductal carcinoma based on gene expression profiles of pancreatic ductal cells.

Pancreatic ductal carcinoma (PDC) remains one of the most intractable human malignancies, mainly because of the lack of sensitive detection methods. Although gene expression profiling by DNA microarray analysis is a promising tool for the development of such detection systems, a simple comparison of pancreatic tissues may yield misleading data that reflect only differences in cellular composition. To directly compare PDC cells with normal pancreatic ductal cells, we purified MUC1-positive epithelial cells from the pancreatic juices of 25 individuals with a normal pancreas and 24 patients with PDC. The gene expression profiles of these 49 specimens were determined with DNA microarrays containing >44 000 probe sets. Application of both Welch's analysis of variance and effect size-based selection to the expression data resulted in the identification of 21 probe sets corresponding to 20 genes whose expression was highly associated with clinical diagnosis. Furthermore, correspondence analysis and 3-D projection with these probe sets resulted in separation of the transcriptomes of pancreatic ductal cells into distinct but overlapping spaces corresponding to the two clinical classes. To establish an accurate transcriptome-based diagnosis system for PDC, we applied supervised class prediction algorithms to our large data set. With the expression profiles of only five predictor genes, the weighted vote method diagnosed the class of samples with an accuracy of 81.6%. Microarray analysis with purified pancreatic ductal cells has thus provided a basis for the development of a sensitive method for the detection of PDC.

Screening of genes specifically activated in the pancreatic juice ductal cells from the patients with pancreatic ductal carcinoma.

Pancreatic ductal carcinoma (PDC) is one of the most intractable human malignancies. Surgical resection of PDC at curable stages is hampered by a lack of sensitive and reliable detection methods. Given that DNA microarray analysis allows the expression of thousands of genes to be monitored simultaneously, it offers a potentially suitable approach to the identification of molecular markers for the clinical diagnosis of PDC. However, a simple comparison between the transcriptomes of normal and cancerous pancreatic tissue is likely to yield misleading pseudopositive data that reflect mainly the different cellular compositions of the specimens. Indeed, a microarray comparison of normal and cancerous tissue identified the INSULIN gene as one of the genes whose expression was most specific to normal tissue. To eliminate such a "population-shift" effect, the pancreatic ductal epithelial cells were purified by MUC1-based affinity chromatography from pancreatic juice isolated from both healthy individuals and PDC patients. Analysis of these background-matched samples with DNA microarrays representing 3456 human genes resulted in the identification of candidate genes for PDC-specific markers, including those for AC133 and carcinoembryonic antigen-related cell adhesion molecule 7 (CEACAM7). Specific expression of these genes in the ductal cells of the patients with PDC was confirmed by quantitative real-time polymerase chain reaction analysis. Microarray analysis with purified pancreatic ductal cells has thus provided a basis for the development of a sensitive method for the detection of PDC that relies on pancreatic juice, which is routinely obtained in the clinical setting.