Mutated genes on ctDNA detecting postoperative recurrence presented reduced neoantigens in primary tumors in colorectal cancer cases.

The detection and sequencing of the mutated ctDNA is one of the irreplaceable clinical measures in the postoperative management of colorectal cancer (CRC) cases. However, we are curious to comprehend the essential traits of mutated genes comprising metastatic sites out of whole mutated genes in primary sites. In the current retrospective study, we conducted target resequencing of ctDNA using 47 plasma samples and established a cancer panel carrying the commonly mutated genes between primary and recurrent tumors. We found that mutated genes in ctDNA indicated immune-resistance traits with respect to the impaired ability to present neoantigens by loss of expression or binding affinity to HLA in the primary tumor. Compared with the estimated neoantigens from all mutated genes in primary tumors, the neoantigen peptides from commonly mutated genes on the panel showed abundant expression but no binding affinity to HLA. Therefore, ctDNA mutations can be frequently and postoperatively detected to identify recurrence; however, these mutated genes were derived from immune-tolerated clones owing to the loss of neoantigen presentation in primary CRC tumors.

Complete Surgical Resection of a Leiomyosarcoma Arising from the Inferior Vena Cava.

A 76-year-old Japanese man was referred to our hospital with chief complaint of right hypochondoralgia. Abdominal ultrasound showed a retroperitoneal tumor in the suprarenal region of the right kidney. Computed tomography revealed an enhanced lobular tumor with irregular, circumscribed, and indistinct border. Ultrasound-guided biopsy was performed. The tumor consisted of spindle-shaped cells with a giant nucleus and multinuclear cells. The diagnosis was leiomyosarcoma by immunohistochemical staining. The patient underwent surgery accessed by a right eighth intercostal thoracoabdominal incision. The tumor was completely resected, accompanied by removal of the posterosuperior segment of the right hepatic lobe, right adrenal gland, and a portion of the inferior vena cava (IVC). The histopathologic diagnosis was leiomyosarcoma arising from the IVC. We present a rare case of a successfully managed leiomyosarcoma of the IVC. This case suggests the importance of curative surgical resection of the tumor due to low efficacy of adjuvant chemotherapy for leiomyosarcoma.

Giant polypoid tumor expressing on the pyloric ring.

A 66-year-old Japanese man was referred to our hospital because of suspected duodenal cancer. Upper gastric endoscopy revealed a giant polypoid-type tumor that extended from the duodenum bulb to the pyloric ring. A computed tomography scan revealed a slightly enhanced lobular tumor protruding into the duodenum bulb. Positron emission tomography showed an accumulation of (18)F-fluorodeoxyglucose in the area extending from the antrum of the stomach to the duodenum bulb. Since an endoscopic ultrasound test suggested that the tumor might invade the muscular tunic, indications of endoscopic mucosal resection were not favored, and the tumor was curatively removed via distal gastrectomy. The histopathologic diagnosis was papillary adenocarcinoma, and the invasion depth was the mucosal layer without vascular invasion, which was different from the preoperative diagnosis. Our case suggests the difficulties in precise diagnosis of the invasion depth of the giant polypoid cancer.

Validation of the Estimation of Physiologic Ability and Surgical Stress (E-PASS) score for maintenance hemodialysis patients undergoing elective abdominal surgery.

AIMS: This study assessed the validity of the Estimation of Physiologic Ability and Surgical Stress (E-PASS) score in maintenance hemodialysis patients undergoing elective abdominal surgery. METHODS: We retrospectively reviewed the medical records of 73 hemodialysis patients who underwent elective gastrointestinal surgery. The main outcomes analyzed were the E-PASS score and postoperative course, which were defined by mortality and morbidity. The discriminative capability of the E-PASS score was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: The overall mortality rate observed was 2.7% (2 patients) and the morbidity rate was 36.9%. There were no significant differences in the comprehensive risk score, preoperative score or surgical stress score for patients with or without complications (p = 0.556, 0.639 and 0.168, respectively). Subsequent ROC curve analysis demonstrated poor predictive accuracy for morbidity. When the results in our study population were compared with those in Haga's study population, our population exhibited a highly significant rightward shift (p < 0.001). CONCLUSION: The E-PASS score was a poor predictor of complications because maintenance hemodialysis patients already have relatively high risk factors. This scoring system should not be applied in such a special group with high risk factors.

Risk factors for maintenance hemodialysis patients undergoing elective and emergency abdominal surgery.

PURPOSE: To identify the risk factors for morbidity and mortality after elective and emergency abdominal surgeries in maintenance hemodialysis patients. METHODS: We retrospectively evaluated the medical records of 63 hemodialysis patients who underwent elective (group 1) and 24 who underwent emergency (group 2) abdominal surgeries, and classified them according to the presence/absence of postoperative complications. The clinical, laboratory and procedure-related data were obtained and compared between the groups. RESULTS: Group 2 had significantly higher morbidity and mortality rates than group 1 (58.3 and 16.6 % vs. 33.3 and 16.6 %, respectively, P < 0.05). The patients in group 1 with and without complications had significantly different blood urea nitrogen (BUN) levels of 52.3 vs. 41.6 mg/dL (P = 0.03). There were significant differences in the patients in group 2 in terms of the age (72.7 vs. 55.0 years old; P < 0.002), the length of the operation (141 vs. 107 min; P < 0.02), the total protein levels (6.2 vs. 6.7 g/dL; P < 0.03), albumin levels (3.2 vs. 3.7 g/dL; P < 0.04) and need for intra- or postoperative blood transfusions (71.4 vs. 10.0 %; P < 0.005). CONCLUSIONS: The risk factors for a poor surgical outcome included high BUN levels in the elective surgery patients and hypoproteinemia, hypoalbuminemia, a longer operation and older age in patients undergoing emergency surgery. Perioperative blood transfusion was also associated with a high complication rate in the emergency surgery group.

Surgical therapy and chemoradiotherapy for postoperative recurrent esophageal cancer.

BACKGROUND/AIMS: A retrospective analysis of therapeutic modalities used in postoperative recurrent esophageal cancer. METHODOLOGY: Among 43 esophageal cancer patients who underwent esophagectomy between 2003 and 2010, recurrence was found in 15. Best supportive care was given to two patients and another patient was referred to another hospital. The remaining 12 patients were treated by the following modalities: Surgical resection: 2 cases; chemoradiotherapy: 7 cases; chemotherapy: 2 cases; and radiotherapy: 1 case. The median survival time, 1-year survival rates, and response rates were examined. Data from 13 esophageal cancer patients who underwent chemoradiotheray as an initial therapy in the same period were collected and compared with recurrent cases treated with chemoradiotherapy. RESULTS: For all 12 patients, the median overall survival time was 19.5 months, and the 1-year survival rate was 83%. Among 7 chemoradiotherapy patients, the response rate was 57%. The median survival time was 23 months, and the 1-year survival rate was 86%. The response rate of 13 patients receiving chemoradiotherapy as an initial therapy was 69%. The median overall survival time was 12 months and the 1-year survival rate was 54%. CONCLUSIONS: Re-operation and chemoradiotherapy for recurrent esophageal cancer might be as effective as the same treatment used initially.

Physiological evaluation of residual stomach motility after local resection in conscious dogs.

PURPOSE: To investigate the phenomenon of remnant gastric motility and emptying after local resection. METHODS: Fifteen dogs were divided into three groups: a control (CONT) group, a group that underwent local resection of the greater (GREAT) curvature, and a group that underwent resection of the lesser (LESS) curvature. We conducted a strain gauge force transducer study, a [(13)C]octanoic acid breath test ((13)C-OBT), and a mosapride citrate effect test. Based on these results, we worked out the receptive relaxation (RR), motility index (MI), and postprandial period (PP) in the postprandial state, and the frequency, duration, and MI of phase III in the fasted state. The half emptying time (T (1/2)) of (13)C-OBT was also calculated. The MI was compared according to the mosapride effect test results. RESULTS: Postprandial RR, antro-pyloro-duodenal coordination, and fasting contractions were maintained in all three groups. Receptive relaxation was significantly shorter in the LESS group than in the other groups. Motility index was significantly lower in both treatment groups than in the CONT group. The PP was significantly longer in the GREAT group than in the other two groups. The (13)CO(2) excretion curves did not differ significantly among the groups. The duration of phase III was remarkably less in the treatment groups than in the CONT group, and MI was significantly lower in the LESS group than in the other groups in the fasted state. The MI increased remarkably after mosapride administration in the CONT group, showing no differences in other objective groups. CONCLUSION: Gastric function was maintained after gastric local resection, although its motility decreased.

Sustained aberrant localization of KL-6 mucin and beta-catenin at the invasion front of human gastric cancer cells.

AIMS: This study sought to analyze the clinicopathological significance of KL-6 mucin, a type of MUC1, in gastric cancer and its relationship to ß-catenin. PATIENTS AND METHODS: Subcellular localization of KL-6 mucin and ß-catenin in gastric cancer tissues (n = 96) was detected immunohistochemically and its clinicopathological significance was evaluated. RESULTS: Samples with localization of KL-6 mucin in the surrounding membrane and/or cytoplasm of cancer cells at the invasion front (n = 50, 52%) had a higher incidence of deeper invasion (p < 0.0001), lymphatic vessel invasion (p = 0.0003), venous invasion (p < 0.0001), lymph node metastasis (p < 0.0001) and an advanced TNM stage (p = 0.0005). Furthermore, this localization of KL-6 mucin was associated with accumulated nuclear localization of ß-catenin. CONCLUSION: In concert with aberrant localization of ß-catenin, sustained localization of KL-6 mucin in the surrounding membrane and/or cytoplasm of cancer cells at the invasion front has a significant role in cancer progression.

A case of esophageal cancer with mesojejunal lymph node metastasis after total gastrectomy.

A 56-year-old man was diagnosed with esophageal cancer by upper gastrointestinal endoscopy for examination of dysphagia. The patient had undergone total gastrectomy and jejunal interposition 4 years previously for a gastric cancer at the pT1N0M0 stage according to the UICC-TNM classification. Enhanced CT findings revealed a 3-cm-diameter mass located near the superior mesenteric artery. We conducted subtotal esophagectomy associated with partial jejunectomy including mesojejunectomy. The mass was histologically diagnosed to be mesojejunal lymph node metastasis from esophageal cancer. Mesojejunal lymph node metastasis from esophageal cancer developing after total gastrectomy has been reported in only three cases including ours. The present lymph node metastases may have occurred via the newly developed lymphatic drainage route through the esophagojejunostomy, and this metastatic lymph node can be considered the regional lymph node. Therefore, resection of the interposed jejunal limb with mesojejunectomy may be rational in surgery on esophageal cancer developing after total gastrectomy.

Appearance of high-molecular weight sialoglycoproteins recognized by Maackia amurensis leukoagglutinin in gastric cancer tissues: a case report using 2-DE-lectin binding analysis.

Aberrant expression of sialoglycoconjugates has been thought to play an important role in cancer progression. Our previous lectin-histochemical study showed that overexpression of sialoglycoconjugates recognized by alpha2,3-sialic acid-specific Maackia amurensis leukoagglutinin (MAL) was significantly related to the malignancy of gastric cancer. The present study analyzed the sialoglycoproteins in gastric cancer tissues by 2-dimensional electrophoresis (2-DE) in combination with lectin-binding analysis using MAL. Various MAL-positive sialoglycoproteins were detected in cancer tissues but not in non-cancer tissues. The sialoglycoproteins have a high molecular weight of near 200 kDa and over 200 kDa with different pI values for the two. This suggests that the MAL-positive sialoglycoproteins detected in gastric cancer tissues have high molecular weights and may contain different numbers of alpha2,3-linked sialic acid residues in the carbohydrate moiety.

Stomach-partitioning gastrojejunostomy for gastroduodenal outlet obstruction.

HYPOTHESIS: The outcome of the stomach-partitioning gastrojejunostomy (SPGJ) procedure is superior to that of stenting procedures. DESIGN: Data from patients who underwent an SPGJ were collected retrospectively from hospital medical records (body weight, hemoglobin and albumin levels, assessment of food intake, duration of hospitalization, complications, and survival rates), and we compared the results with those obtained from patients treated with stenting. SETTING: Departments of Gastrointestinal Surgery and Gastroenterology, Tokyo University Hospital, Tokyo, Japan. PATIENTS: A series of 16 consecutive patients with gastroduodenal outlet obstruction who underwent an SPGJ and 9 patients who were treated with stenting between January 5, 1998, and August 18, 2004. MAIN OUTCOME MEASURES: Mann-Whitney, Fisher exact, and generalized Wilcoxon tests were used for statistical analyses. RESULTS: There were no differences between the 2 groups concerning background data, physiological status, or laboratory data. The starting point of food intake by patients treated with stenting was significantly earlier (at 4.2 days in the stent group vs at 6.0 days in the SPGJ group, P < .004). The numbers of patients taking a regular meal at 2 weeks after treatment were 12 of 16 patients in the SPGJ group and 1 of 9 patients in the stent group (P < .001). There was no significant difference between the 2 groups regarding the duration of hospitalization. The complication rates were significantly different between the 2 groups (P = .48). The median survival was 7.3 months in the SPGJ group and 2.8 months in the stent group (P = .008), and the mean 6-month survival rates were 81% (13 of 16) and 33% (3 of 9), respectively (P < .04). CONCLUSION: Stomach-partitioning gastrojejunostomy achieved improved quality of life and a better prognosis compared with stenting procedures, and it is the treatment of choice for gastroduodenal outlet obstruction.

Nutritional comparisons between a pylorus-preserving gastrectomy with and without suprapyloric lymph node clearance: a preliminary report.

BACKGROUND/AIMS: A pylorus-preserving gastrectomy (PPG) is a procedure for gastric cancer (GC) patients which attempts to control gastric emptying and to minimize postoperative nutritional disadvantages. The persistence of conflicting stances concerning qualifying candidates for PPG--a narrower or wider segment of patients--is attributable to a lack of decisive evidence concerning the precise nutritional impact of suprapyloric lymph node clearance. METHODOLOGY: Forty-eight patients underwent a PPG with (30 patients; dissection group) or without (18 patients; preservation group) suprapyloric lymph node clearance between 2002 and 2004. Patients with mucosal GC located in the middle third of the stomach were assigned to the preservation group and the other early GC patients formed the dissection group. Those who were followed up more than one year postoperatively were selected from the preservation (8 patients) and the dissection (16 patients) groups, and changes in body weight, hemoglobin, total protein, and albumin were compared between the two groups. Baseline clinicopathological characteristics, surgically related events, and supportive medications were also compared between the two groups. RESULTS: Dissection group patients received significantly longer surgery (p < 0.01) and a wider scope of lymphadenectomy (p < 0.0001) than preservation group patients. Other factors including the length of postoperative hospital stay and morbidity rate did not differ between the two groups. Percent changes in body weight, hemoglobin, total protein, and albumin, as well as postoperative profiles of each parameter were similar between the two groups. CONCLUSIONS: These results suggest that suprapyloric lymph node clearance resulted in more traumatic surgery while it did not exacerbate postoperative nutritional status as compared with suprapyloric lymph node preservation. PPG is justifiable for submucosal GC or an even wider segment of patients by suprapyloric lymph node clearance without nullifying the anticipated nutritional benefit.

The intergroup/RTOG 85-01 concurrent chemoradiation regimen for Japanese esophageal cancer.

BACKGROUND/AIMS: To evaluate outcome of the U.S. RTOG/Intergroup Protocol 85-01 for 44 Japanese esophageal cancer patients. METHODOLOGY: Between 1996 and 2004, patients with esophageal cancer received the Intergroup concurrent chemoradiation therapy regimen for the primary treatment (n=44, group A). We compared the data with those of patients receiving radiotherapy (RT) combined with the weekly chemotherapy regimen (n=12, group B) and with those of patients receiving RT combined with the daily low-dose chemotherapy regimen (n=24, group C). RESULTS: The median survival period was 14.9 months in group A, 5.7 months in group B, and 6.3 months in group C. The survival rates at 1 and 3 years were 56% and 26% in group A, 42% and 21% in group B (p=0.3307), and 27% and 18% in group C (p=0.0462), respectively. CONCLUSIONS: The prognosis of patients who received the Intergroup regimen for esophageal cancer was significantly better than that of patients who received the daily low-dose chemotherapy regimen. The Intergroup regimen is well tolerable for the Japanese patients too.

Helicobacter pylori-negative / API2-MALT1 translocation-negative low-grade MALT lymphoma.

A 71-year-old man with a Helicobacter pylori infection-negative and API2-MALT1 translocation-negative extranodal marginal-zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type of the stomach has been followed conservatively for over 5 years. The lesion has shown no major morphological changes or malignant progression into a diffuse large-cell type during the time course. The absence of genetic translocation of API2-MALT1 was confirmed with fluorescence in situ hybridization (FISH). The prognosis of H. pylori-negative and API2-MALT1 translocation-negative low-grade MALT lymphoma is unknown, and a standard treatment for such lymphoma has yet to be defined. The case of MALT lymphoma negative for both of the above factors that we report has shown no obvious rapid progression or malignant change over the long-term course. Although curative operation and/or chemoradiotherapy should still be discussed as the treatment of choice, the treatment of this type of lymphoma must be carefully determined on a case-by-case basis, according to its biological status and prognosis.

Treatment results of preoperative concurrent chemoradiotherapy followed by surgery for stage III or IV esophageal squamous cell carcinoma.

PURPOSE: To evaluate the treatment outcome of preoperative neoadjuvant radiotherapy combined with chemotherapy (CTx) for 17 esophageal cancer patients. MATERIALS AND METHODS: Between 1992 and 2004, patients with locally advanced esophageal cancer (stage III or IV) before curative-intent surgery received radiotherapy (RT) combined with CTx (Cisplatin: 75 mg/m2, bolus infusion, and 5-fluorouracil (5-FU): 1,000 mg/m2/24 h, continuous infusion for 4 days) at a median total dose of 30 Gy (n=17). RESULTS: The median survival period was 13.8 months. The overall survival rates at 1, 2, and 3 years were 75%, 40%, and 20%, respectively. According to univariate analysis, no factor of worse prognosis was found. Pathological markedly (Grade 3) or moderately (Grade 2) effects were observed in 4 patients (24%) and 8 patients (47%), respectively. CONCLUSION: These results indicate that, although this regimen was effective in terms of pathological effect, it is unclear whether it made a contribution to the improvement of survival

Safety of a paraaortic node dissection for selected advanced gastric cancer patients.

BACKGROUND/AIMS: Comprehensive evaluations of a superextended (D3) dissection concerning its benefits as well as potential disadvantages have been scanty in the English literature. METHODOLOGY: The patient selection criteria for a D3 dissection were pre- and intraoperatively > or = T3 and/or > or = N2 diseases, no paraaortic node involvement, no distant or peritoneal metastases, and a negative peritoneal lavage cytology. A D3 dissection involved a node clearance up to the third tier including the middle paraaortic region. Twenty-seven patients were entered into our D3 dissection strategy in a prospective manner between 1997 and 2000, and were divided into 2 groups: pathologically meeting the D3 criteria (D3 criteria fit; 12 patients) and pathologically proved to have less advanced disease (less advanced/D3; 15 patients). Data from age-matched 53 patients who underwent a D2 dissection between 1991 and 1996 were collected and also divided according to the current D3 criteria. Surgical invasiveness, morbidity and mortality, nutritional parameters, and survival were compared between D2 and D3 patients. Additionally, positive paraaortic node patients with a D3 dissection (4 patients) were used for preliminary survival comparison. RESULTS: A D3 dissection resulted in longer surgery and more blood loss, but morbidity and mortality, and nutritional impairment were similar to those of a D2 dissection. A more promising survival rate by a D3 dissection over a D2 dissection was observed only in the D3 fit patients but not in the less advanced disease patients. On the contrary, survivals of the positive paraaortic node patients were pessimistic despite the R0 resection. CONCLUSIONS: A D3 dissection is an invasive procedure but can be performed as safely as a D2 dissection. Our results provide a starting point for a D3 challenge; however, paraaortic node positive patients should be excluded from a D3 dissection.

Performance of outpatient regimen of S-1 in combination with fractional cisplatin for advanced or recurrent gastric cancers: a phase I study.

BACKGROUND: We designed an outpatient regimen consisting of fractional cisplatin in combination with S-1, a novel oral fluoropyrimidine derivative for the treatment of recurrent or advanced gastric cancer and conducted a phase I study to determine the dose limiting toxicities (DLTs) and recommended dose (RD). METHODS: Escalating dosages of cisplatin (15, 20, and 25 mg/m(2), as levels 1, 2, and 3, respectively) were administered over 2 h on days 1, 8, and 15, with a fixed dose of S-1 for 3 consecutive weeks (days 1-21), repeated every 5 weeks. National Cancer Institute common toxicity criteria(NCI-CTC) grade 2 toxicities required treatment delay. Primary first cycle DLTs were defined as NCI-CTC grade 3 or 4 toxicities (except for hemoglobin levels, nausea, and vomiting). RESULTS: Nine patients were initially enrolled, and DLTs did not appear; however, one level-3 patient experienced grade 3 anemia. An additional three patients were enrolled in level 3 to confirm the toxicity profiles, and none experienced DLTs. Toxicity evaluations throughout a total of 62 cycles revealed that grade 1 or 2 hematological toxicities were common, although mostly transient, with recovery without specific treatment. One patient each in levels 1 and 3 required hospitalization due to grade 3 toxicities in the later cycles. Mean dose intensities for S-1 and cisplatin were both more than 91%. There were no treatment-related deaths. The preliminary response rate was 44%. CONCLUSIONS: It was concluded that the RD of cisplatin in this regimen was 25 mg/m(2) (level 3). S-1 in combination with fractional cisplatin is a promising regimen that allows repeated drug administration, in an outpatient setting, for advanced or recurrent gastric cancers. A phase II study of the RD is now under way.

[Barrett's adenocarcinoma].

Esophageal adenocarcinoma has seen a rapid increase in incidence throughout the Western world. Gastroesophageal reflux disease is an important risk factor for this cancer that develops in patients with Barrett's esophagus, but infection with Helicobacter pylori may reduce the risk. The diagnosis of Barrett's adenocarcinoma is often at an advanced stage and is generally associated with a poor prognosis. Several innovative techniques (eg, chromoendoscopy, magnifying endoscopy, and narrow-band imaging) have recently been developed to improve the accuracy of diagnosis. Although surgical resection has been a mainstream treatment for advanced cancer, endoscopic submucosal dissection is becoming a promising treatment procedure for mucosal cancer. Surveillance, endoscopic ablative therapies, chemoprevention, and anti-reflux surgery have been developed for cancer prevention, but are of unproven value. Further evaluation is warranted to define the optimal method and standardize the procedures for diagnosis and management of Barrett's esophagus.

Chemopreventive effect of peroxisome proliferator-activated receptor gamma on gastric carcinogenesis in mice.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is known to be expressed in several cancers, and the treatment of these cancer cells with PPARgamma ligands often induces cell differentiation and apoptosis. Recently, the chemopreventive potential of PPARgamma ligands on colon carcinogenesis was reported, although the effect of PPARgamma on colon carcinogenesis and the mechanism of the effect remain controversial. In this study, we attempted to elucidate the role of PPARgamma in gastric carcinogenesis and explored the possible use of PPARgamma ligand as a chemopreventive agent for gastric cancer. N-methyl-N-nitrosourea (MNU, 240 ppm) was given in drinking water for 10 weeks to induce gastric cancer in PPARgamma wild-type (+/+) and heterozygous-deficient (+/-) mice, followed by treatment with PPARgamma ligand [troglitazone, 0.15% (w/w) in powder food] or the vehicle alone for 42 weeks. At the end of the experiment, PPARgamma (+/-) mice were more susceptible to MNU-induced gastric cancer than wild-type (+/+) mice (89.5%/55.5%), and troglitazone significantly reduced the incidence of gastric cancer in PPARgamma (+/+) mice (treatment 55.5%/vehicle 9%) but not in PPARgamma (+/-) mice. The present study showed that (a) PPARgamma suppresses gastric carcinogenesis, (b) the PPARgamma ligand troglitazone is a potential chemopreventive agent for gastric carcinogenesis, and (c) troglitazone's chemopreventive effect is dependent on PPARgamma.