Search

Purpose: This study aimed to investigate the abilities of the modified Glasgow prognostic score (mGPS) and other inflammatory scores to predict recurrence-free survival (RFS) among patients with colon cancer (CC). In addition, we evaluated the abilities of the mGPS to predict recurrence of stage II disease and the efficacy of adjuvant chemotherapy (AC) for stage III disease., Methods: This retrospective study evaluated 477 patients with stage I-III CC who underwent curative surgery. These patients were categorized as having a low mGPS (mGPS 0) or a high mGPS (mGPS 1-2)., Results: Patients in the high mGPS group had significantly poorer RFS than patients in the low mGPS group (p < 0.01). Multivariate analysis revealed that a high mGPS independently predicted poor RFS (p < 0.01). Among patients with stage II CC, multivariate analysis revealed that the independent predictors of poor RFS were pT4 status (p < 0.01) and a high mGPS (p = 0.04). Among patients with stage III CC, AC was not significantly associated with the 5-year RFS for patients with a low mGPS (p = 0.38), although AC significantly improved the 5-year RFS for patients with a high mGPS (p < 0.01)., Conclusion: The preoperative mGPS significantly predicted recurrence among patients with CC, even among patients with stage II CC. In addition, mGPS may provide valuable information regarding subgroups of patients with stage III CC who might benefit from AC.

Background/aim: The present study aimed to clarify an accurate diagnostic method for lymph node metastasis (LN+) in rectal neuroendocrine tumors (rNETs)., Patients and Methods: This was a retrospective study of 14 rNETs and 45 rectal adenocarcinoma patients undergoing rectal resection. The short axis of LNs was measured using CT and pathological findings (43 paraffin-fixed LNs in rNETs and 786 LNs in adenocarcinoma)., Results: The size of LN+ in CT and pathological findings was smaller in rNETs than adenocarcinoma (p=0.082 and p<0.001, respectively). The AUC values of ROC curves for detecting LN+ using LN sizes on CT were 0.837 for rNETs and 0.885 for adenocarcinoma (Cut-off values: 5 mm for rNETs, 7 mm for adenocarcinoma). rNETs were diagnosed with high accuracy using the cut-off value of rNETs (5 mm) (sensitivity: 80.0%, and specificity: 87.5%)., Conclusion: The size of LN+ was smaller in rNETs than in adenocarcinoma, suggesting the essentiality of diagnostic criteria specific for rNETs., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The case is a 73-year-old man who underwent esophagectomy and retrosternal gastric conduit reconstruction for esophageal cancer. Reoperation was performed because the oral side of the gastric tube developed necrosis on the 31st postoperative day. The necrotic parts of the gastric tube were resected, and a cervical esophageal stoma was created. The remaining gastric tube was pulled up at the anterosternal subcutaneous location in preparation for the two-stage reconstructive operation. The reconstructive operation with a free jejunum graft through the anterosternal subcutaneous route was performed 35 days after the reoperation. Vascular anastomosis was performed with the right internal thoracic artery and vein by microsurgery. The postoperative course was satisfactory. Necrosis of the gastric tube is a rare and severe complication of esophagectomy. Reconstructive surgery for gastric tube necrosis is generally necessary but difficult to perform because of the severe surgical stress it confers on the patient. In this paper, we showed a new approach for two-stage reconstruction with a free jejunum graft through the anterosternal subcutaneous route. This operative procedure causes relatively less surgical stress than other procedures; hence, it is considered to be a beneficial reconstructive approach for patients with gastric tube necrosis.

A 67-year-old man was admitted to our hospital because of a type 2 tumor on the posterior wall of the cardia, and a biopsy resulted in a diagnosis of moderately differentiated tubular adenocarcinoma. Abdominal CT revealed swelling of the No. 1, 3, 11p(bulky N), and No.16a2lat lymph nodes. He was diagnosed with gastric cancer, T4aN2M1(LYM), cStage ⅣB, and was administered chemotherapy. After 2 courses of chemotherapy containing capecitabine plus cisplatin(XP), both the primary tumor and lymph nodes markedly decreased in size; then, total gastrectomy with D2+No.16a2lat was performed. Pathological examinations showed no residual cancer cells both in the primary lesion and lymph nodes; thus, the treatment effect of chemotherapy was Grade 3. Some gastric cancer patients may undergo curative resection even with extensive lymph node metastases when effective chemotherapy has been administered. Further discussions are needed about optimal chemotherapeutic regimens and surgical procedures.

A 68-year-old man was diagnosed with esophagogastric junction adenocarcinoma, cT4a(SE)N3aM0, cStage Ⅲ. Because "bulky N" was present, he was administered 2 courses of preoperative chemotherapy containing S-1 plus oxaliplatin(SOX). Both the primary tumor and enlarged lymph nodes had greatly decreased in size following chemotherapy, and total gastrectomy and lower esophagectomy with D2 lymphadenectomy were then performed. Histopathological examinations showed no residual cancer cell both in the primary lesion and dissected lymph nodes; thus, the efficacy of the chemotherapy was Grade 3. Preoperative chemotherapy containing SOX could be one of the useful treatment options for gastric cancer patients with extensive lymph node metastases including "bulky N".

Anal canal adenocarcinoma with pagetoid spread has different a treatment strategy and prognosis from extramammary perianal Paget disease. We report two cases of anal canal adenocarcinoma with pagetoid spread along with a literature review. Case 1: A 69-year-old woman complained of perianal pain, redness, and erosion. Biopsy revealed adenocarcinoma with pagetoid spread. Laparoscopic abdominoperineal resection was performed, which resulted in 12 months' survival without postoperative recurrence. Case 2: A 62-year-old man complained of fecal occult blood and hemorrhoid. Under the diagnosis of anal canal cancer, transanal tumor resection was performed. Five years after surgery, he underwent endoscopic submucosal dissection for anal canal cancer. Ten years after surgery, he complained of anal tumor and perianal redness. Biopsy revealed adenocarcinoma with pagetoid spread. Laparoscopic abdominoperineal resection was performed, which resulted in 10 months' survival without postoperative recurrence.

Case 1 was that of a 65-year-old woman. Radical esophagectomy was performed after neoadjuvant chemotherapy(NAC) for lower thoracic esophageal cancer. Nineteen months after surgery, local recurrence was indicated on the dorsal side of the descending aorta. After chemoradiotherapy(CRT)and chemotherapy, residual cancer with aortic invasion was diagnosed. Case 2 was that of a 64-year-old man. Radical esophagectomy was performed after NAC for middle thoracic esophageal cancer. Five months after surgery, local recurrence was indicated between the descending aorta and left inferior pulmonary vein. After CRT and chemotherapy, residual cancer with invasion of the aorta and left lung was diagnosed. In both cases, we inserted an aortic stent and safely performed residual cancer resection including the aortic adventitia. In summary, aortic stent insertion enables safe resection of local recurrent tumors in the aorta after radical esophagectomy.

YEATS domain containing 4 (YEATS4) has functions of chromatin modification and transcriptional regulation and is in a gene-amplified region (12q13) in various human cancers. In this study, we tested whether YEATS4 acts as a cancer-promoting gene through its activation/overexpression in gastric cancer (GC). We analyzed 5 GC cell lines and 135 primary tumor samples of GC, which were curatively resected in our hospital. Overexpression of the YEATS4 protein was frequently detected in GC cell lines (5/5 cell lines, 100%) and primary GC tumor tissues (32/135 cases, 23.7%). Knockdown of YEATS4 inhibited proliferation, migration and invasion of GC cells through NOTCH2 down-regulation in a TP53 mutation-independent manner, and induced apoptosis in wild-type TP53 GC cells. Moreover, knockdown of YEATS4 improved chemosensitivity for CDDP and L-OHP. Overexpression of YEATS4 protein significantly correlated with more aggressive lymphatic invasion, larger tumor size, deeper tumor depth, positive lymph node metastasis and recurrence. Patients with YEATS4-overexpressing tumors had a lower overall survival rate than those with non-expressing tumors. Multivariate analysis demonstrated that YEATS4 was independently associated with poor outcomes. These findings suggest that YEATS4 plays a pivotal role in tumor malignant potential through its overexpression and highlight its usefulness as a prognostic factor and potential therapeutic target in GC., Competing Interests: None.

A 42-year-old woman with complaints of fever and abdominal pain, was diagnosed to have perforative appendicitis, for which emergency surgery was performed. Marked thickening and edema around the cecum, ileum, and the mesentery was observed. Ileocecal resection was performed, as malignant disease could not be excluded. Histopathological examination revealed abscess formation in the lining membrane of the intestine, inflammatory granulation and proliferation of the spindleshaped cells in the serosal membrane extensively, and an inflammatory pseudotumor(IPT)was diagnosed. It is generally difficult to clearly distinguish IPT from a malignant tumor before surgery. We thus report this case, along with a review of literature.

Nucleophilic 5-endo-trig cyclisation was achieved in 2,2-difluorohomoallylic alcohols. Upon treatment with potassium hydride, 2,2-difluorohomoallylic alcohols underwent an intramolecular SN2'-type reaction to afford 3-fluoro-2,5-dihydrofurans in high yields. In addition, the oxidation of these dihydrofurans formed 4-fluorofuran-2(5H)-ones. Thus, ring-fluorinated furan derivatives were efficiently obtained via allylic sp3 carbon-fluorine bond cleavage.

Background: Preoperative precise staging is essential for the treatment of gastric cancer (GC); however, the diagnostic accuracy of conventional modalities needs to be increased. The present study investigated the clinical value of positron emission tomography-computed tomography (PET-CT) for the staging of GC., Methods: This was a retrospective study of 117 patients with a clinical diagnosis of advanced GC who underwent PET-CT followed by gastrectomy. The incidence of FDG uptake in the primary tumor or lymph nodes and its relationship with clinicopathological factors, particularly pathological stage (pStage) III/IV, were examined., Results: FDG uptake in the primary tumor was noted in 83 patients (70.9%). FDG uptake in the lymph nodes was detected in 21 patients (17.9%), and its sensitivity and specificity for lymph node metastasis were 22.7 and 90.5%, respectively. Multiple logistic regression analyses showed that FDG uptake in the primary tumor (odds ratio (OR) 2.764; 95% confidence interval (CI) 1.104-7.459, p = 0.029) and that in the lymph nodes (OR 4.660; 95% CI 1.675-13.84, p = 0.003) were factors independently associated with pStage III/IV. FDG uptake in the primary tumor detected pStage III/IV with higher sensitivity (80.4%) and that in lymph nodes found pStage III/IV with higher specificity (88.7%) than those of upper endoscopy plus CT (60.9 and 67.6%, respectively)., Conclusions: PET-CT appears to be a useful complementary modality in the assessment of pStage III/IV because of the high sensitivity of FDG uptake in the primary tumor and the high specificity of FDG uptake in the lymph nodes.

Curative resection is necessary to survival in pancreatic cancer, however after surgery, pathologic examination sometimes diagnoses the remains of cancer at the resected stump. Therefore, it is necessary to evaluate the stump by intraoperative rapid pathological examination. 5-aminolevulinic acid(5-ALA)is an endogenous natural amino acid and precursor of the heme pathway. 5-ALA is metabolized and accumulated as protoporphyrin IX(Pp IX)that is photosensitive substance. 5-ALA mediated photodynamic diagnosis(PDD)(ALA-PDD)has high diagnostic ability. Andwe previously reportedusefulness of ALA-PDD for lymph node metastasis and peritoneal dissemination in gastric cancer and colorectal cancer patients. A case was 73-year-oldman who hadpancreatic headcancer. Since pancreatic cancer invasion to the inferior vena cava(IVC)was suspected during the operation, fluorescence observation was undergone. Pp IX fluorescence signal observedin the tissue around IVC by fluorescence observation. And, the tissue diagnosed adenocarcinoma by pathological findings. Therefore, it was judged that curative resection was difficult and the operation was completed. In conclusion, it was suggested that ALAPDD may be one of the methods of intraoperatively diagnosing the residual lesion of pancreatic cancer.

Differentiating primary Paget's disease from secondary Paget's disease, which is also known as Pagetoid growth of other cancers, in the perianal region is difficult. Given that the treatment strategies of both disease are significantly different, diagnosis of such conditions should be performed with caution. We report a case of secondary Paget's disease. A 76-year-old man previously visited a hospital because of erythematous plaque around the anus. It was diagnosed as extramammary Paget's disease based on skin biopsy results; consequently, perianal skin resection was performed. Pathological examination of the resected specimen indicated Pagetoid growth of mucinous carcinoma, and it was positive for stump. Consequently, laparoscopic abdominoperineal resection was performed. Finally, the plaque was diagnosed as anal canal adenocarcinoma with Pagetoid growth, and all the previous results were deemed as initial diagnosis., Conclusion: Discriminating between primary and secondary Paget's disease, even with immunohistological techniques, is difficult. Novel methodology that might facilitatemoreaccuratediagnosis preoperatively for erythematous plaquearound theanus and morecurativethe rapeutic strategy are needed.

Neoadjuvant chemotherapy(NAC)has been proven to have survival benefit for patients with resectable advanced esophageal squamous cell carcinoma(ESCC). Among a total of 208 patients with ESCC who underwent radical surgery following NAC between March 2000 and January 2017, 6 patients achieved histologically complete response. Before NAC, the average major axis length of the tumor was 57 mm, and the clinical stages were Stage II (2 patients)and Stage III (4 patients). FP therapy(cisplatin and 5-fluorouracil)was administered to 4 patients, and DCF therapy(docetaxel, cisplatin, and 5-fluorouracil) to 2 patients. Five patients showed partial response(PR)and 1 showed stable disease(SD). The average number of days between NAC and surgery was 26.2(16-44). Postoperative complications were observed in 2 patients(anastomotic leakage and recurrent nerve paralysis). There was no treatment-related mortality. All patients are surviving without relapse. The present study indicated that DCF therapy for patients with resectable advanced ESCC prior to surgery could further improve prognosis.

This study aimed to examine the clinicopathological factors and prognoses of 5 patients with Stage IV gastric cancer(GC) who underwent chemotherapy followed by R0 resection at our institute from 2004 to 2013. Two patients had non-regional lymph node metastases, another 2 patients had peritoneal disseminations, and 1 patient had peritoneal dissemination and non-regional lymph node and left adrenal metastases. All patients underwent R0 resections following 2-6 courses of chemotherapy using multiple anticancer drugs. The disappearance of GC cells in non-regional lymph nodes and peritoneal nodules was confirmed. Clavien-Dindo II or less postoperative complications were found in 3 patients, but no perioperative mortality was observed. The histological response of the primary tumor to preoperative chemotherapy was determined as grade 1b or higher in every case. Although GC recurrence was found in 3 patients, 2 patients are alive without any recurrence. The median survival time of 5 patients was 28(range: 14-61)months. Some patients with Stage IV GC could achieve long-term survival due to chemotherapy followed by R0 resection.

Since the national insurance to use oxaliplatin(L-OHP)for gastric cancer was approved in Japan, patients with advanced or recurrent gastric cancer have been treated by CapeOX therapy as one of the standard regimens. Here, we report a case of long-term complete response of peritoneal recurrence from advanced gastric cancer using CapeOx therapy following radical gastrectomy. The patient underwent total gastrectomy with curative intent for advanced gastric cancer with cytology positive, and received S-1 based adjuvant chemotherapy for 13 months. However, tumor marker elevation and peritoneal recurrence were detected by following examinations. The patient received capecitabine, which is a 5-FU prodrug, plus L-OHP therapy. Complete disappearance of peritoneal recurrence was confirmed under laparotomy after the 8th course. L-OHP-induced upregulationof thymidine phosphorylase(TP)was reported to enhance the effectiveness of capecitabine in vivo. CapeOX therapy was also an effective treatment strategy for recurrence following S-1 based chemotherapy.

A 39-year-old woman visited our hospital because of epigastric pain. Gastrointestinal endoscopy revealed a gastric submucosal tumor, 30mm in size, with ulcer locating near to the esophagogastric junction, and it was diagnosed with GIST by the endoscopic ultrasonography-guided fine needle aspiration. Then, she underwent laparoscopic surgery for the removal of gastric GIST. After peeling around the upper stomach, the local resection of the stomach was performed with linear staplers in the minor axis direction under the vision of the endoscope and laparoscope. Histopathological examinations confirmed that the tumor was GIST with an intermediate risk, and all surgical margins were free of GIST cells. Local resection with the laparoscopy endoscopy cooperative surgery(LECS)technique is a very useful way of the removal of gastric GISTs locating near to the esophagogastric junction in terms of the remnant gastric functions. Meanwhile, because the standard LECS requires the opening of the gastric lumen, there remains concerns about the intraperitoneal tumor dissemination for the gastric GIST with ulcer. We herein reported a case of laparoscopic local resection for a gastric GIST with ulcer locating near to the esophagogastric junction without gastric opening.

A 65-year-old woman with a history of pylorus-preserving gastrectomy(PPG)for early gastric cancer visited our hospital because of vomiting. Gastrointestinal endoscopy revealed a large bezoar in the anastomotic site of the stomach. Because the bezoar was too large to be collected orally, the dissolution therapy with taking Coca-Cola®was continued. On the 3rd day after hospitalization, she felt acute abdominal pain with vomiting. Computed tomography revealed intestinal obstruction by a mass with air bubbles inside in the ileum. Emergency operation was performed under a diagnosis of intestinal obstruction due to the bezoar. The black brown bezoar sized 80×35×30mm was extracted through an ileotomy. The delayed gastric empty is considered to involve in the bezoar formation. Therefore, the appropriate education of diet and periodic endoscopic screening are necessary for patients with large amounts of gastric residues especially after PPG. In the dissolution therapy, physicians need to be careful of intestinal obstruction by a bezoar.

The patient was a 66-year-old man who was diagnosed with a type 3 lesion in the esophago-gastric junction and a type 1 lesion in the upper esophagus. Both the lesions were diagnosed as adenocarcinoma. Chest and abdominal computed tomography examinations pointed out No. 106recL lymph node metastasis. He was diagnosed with Stage III esophago-gastric cancer( T2N3M0)and treated by a laparoscopic subtotal esophagectomy with 2-field lymph node dissection. The histological diagnosis was type 3 adenocarcinoma in the esophago-gastric junction with intramural metastasis and massive lymph node metastasis(No. 1, No. 2, No. 101L, No. 106recL). A vertical connection of venous invasion in the submucosal layer was also observed from the primary lesion to the cervical esophagus via intramural invasion. Treatment based on esophageal cancer is necessary in advanced esophago-gastric cancers with intramural metastasis or massive venous invasion.

Background/aim: This study aimed to investigate the efficacy of additional surgical resection (ASR) after endoscopic submucosal dissection (ESD) for superficial esophageal cancer (SEC)., Patients and Methods: Clinicopathological features and prognoses were analyzed in esophageal cancer (EC) cases with the indication for additional treatments (AT) after ESD (37 cases) and in cases that underwent primary resection (13 cases)., Results: Sixteen out of 37 cases underwent ASR. The remaining 21 cases underwent other treatments or observation. Although all ASR cases are alive without recurrence, recurrence developed in 2 non-ASR cases. Residual tumors were detected in 2 ASR cases. All 4 cases were T1b and positive for lymph vessel invasion (ly+). No significant difference was observed in surgical outcomes between ASR and primary surgical resection (PSR) cases., Conclusion: AT need to be considered for T1b and ly+ cases, and ASR is one of the effective AT. The safety of ASR was similar to PSR for SEC., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Extended indications for endoscopic resection for early gastric cancer (EGC) have been widely accepted. However, according to current guidelines, additional gastrectomy with lymph node dissection (LND) is recommended for patients proven to have potential risks of lymph node metastasis (LNM) on histopathological findings. The aim of this study was to elucidate the risk stratification of outcome and LNM according to the number of factors that meet the inclusion criteria for radical LND for possible LNM (LNM risk factors) in patients with negative endoscopic resection margin., Methods: We enrolled 511 EGC patients whose tumors did not meet the absolute or extended indications for endoscopic resection, and investigated the risk stratification of prognosis and LNM according to the total number of LNM risk factors., Results: Recurrence-free and overall survival rates were significantly higher in patients with fewer LNM risk factors for surgical indication (p = 0.0274 and 0.0002, respectively; log-rank test), and the total number of LNM risk factors and frequency of LNM were significantly correlated (p < 0.0001; Kruskal-Wallis test). When only one LNM risk factor was satisfied, the LNM ratio was 0.58 % (1/173, 95 % confidence interval 0.01-3.18)., Conclusion: The present study suggested the possibility of using further minimally invasive treatment strategies based on the total number of LNM risk factors.

Background and Objectives: Little is known about sex-based differences in morbidity and prognosis after gastrectomy for gastric cancer. This study was designed to detect risk factors for severe postoperative complications and define prognosis according to sex after gastrectomy for gastric cancer., Methods: Consecutive patients comprising 878 male and 421 female patients, who underwent R0 gastrectomy for Stage I - III gastric cancer, were retrospectively analyzed. We defined patients with severe postoperative complications as those with anastomotic leakage, a pancreatic fistula, and/or an intra-abdominal abscess of grade> II according to the Clavien-Dindo classification., Results: There was a significant association between sex and severe postoperative complications after gastrectomy for gastric cancer. In the male patients, poor nutrition, open surgery, and disease progression were independent risk factors for severe postoperative complications. In female patients, disease progression was the only independent risk factor. Regarding prognosis, poor nutrition was the only independent poor prognostic factor in male patients., Conclusions: Risk factors for severe postoperative complications were different between the male and female patients. Particularly in male patients, careful nutritional support may be required to prevent severe complications and improve the prognosis.

A 37-year-old man visited a previous hospital because of left abdominal pain. A contrast-enhanced CT scan revealed a 7 cm solid tumor in the pancreas body, and the patient was referred to our hospital. EUS-FNA showed that the tumor cells were positive for b-catenin in the nuclei, as well as for CD10 and CD56. On the other hand, the cells were negative for chromogranin A and synaptophysin. This is the typical immunohistochemical pattern of a solid pseudopapillary neoplasm(SPN). Therefore, we diagnosed this case as SPN before surgery. As the tumor progressed rapidly in 2 months, we performed distal pancreatectomy, total gastrectomy, and partial liver resection of the left lateral segment because of suspicious invasion of the pancreatic tumor to the stomach and the liver. On histological examination of the resected specimen, tumor invasion to the stomach was apparent, but the tumor did not invade the liver. Immunohistochemical staining showed the same SPN pattern as the EUS-FNA results. We identified small and uniform tumor cells, although no pseudopapillary pattern was observed with HE staining. Finally, we diagnosed this case as an undifferentiated carcinoma. We need to consider the possibility of malignant transformation or undifferentiated carcinoma even when a tumor is diagnosed as SPN on EUS-FNA.

Background/aim: Tumor biomarkers, such as carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA19-9), are used to screen and monitor tumor recurrence in patients with colorectal cancer (CRC). 5-Aminolevulinic acid (5-ALA) is used in photodynamic diagnosis and therapy. Porphyrins produced by tumor cells are excreted in the urine after 5-ALA administration. In this study, we evaluated the use of porphyrins as novel tumor markers in urine samples from patients with CRC., Patients and Methods: Porphyrin metabolite concentrations were measured in urine samples of 33 patients with CRC, 16 patients with benign disease and 8 healthy adults, after 5-ALA administration., Results: The porphyrin metabolite concentrations were significantly increased in the CRC group compared to the control group, while in CRC patients, the porphyrin metabolite concentrations in urine were significantly decreased after surgery., Conclusion: These results suggest that the measurement of porphyrin metabolites in urine may potentially serve as a new screening and recurrence marker for CRC., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: Tolerability, adverse events, and long-term outcomes were compared and analyzed between patients receiving oral anticancer agent-based adjuvant chemotherapy regimen (PO group) and those receiving combination adjuvant chemotherapy with oxaliplatin (OX group), after curative resection of colorectal cancer at our Department., Patients and Methods: The subjects included in the study were 169 patients with stage III colorectal cancer who underwent curative resection and received postoperative adjuvant chemotherapy between June 2007 and October 2014. Fifty-three patients were included in the OX group, while 116 patients were included in PO group., Results: No significant difference was observed in treatment completion rates. No significant difference in either the overall or relapse-free survival rates was observed between the two groups., Conclusion: Oxaliplatin has been shown to improve therapeutic outcomes after curative resection of colorectal cancer. Even compared to oral anticancer agents, oxaliplatin appears to be equal in tolerability and treatment completion rate., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Many cancers are known to be regulated by microRNAs (miRNAs), and the relationships between tissue miRNA expression levels and the amounts of miRNA circulating in the plasma (or plasma miRNA) have been examined in many types of cancers, including digestive tract cancers. The role of plasma miRNAs has yet to be elucidated in detail; therefore a comprehensive analysis of plasma miRNAs using microarrays should assist in establishing the utility of liquid biopsy or companion diagnosis. We here described the 3D-Gene(®) miRNA microarray (TORAY) currently used in our laboratory and introduced a trial application in digestive tract cancer diagnosis.

Background: According to the 14th Japanese Classification of Gastric Carcinoma(JCGC), station No. 1 lymphadenectomy for distal gastrectomy was included in the D1 level, though the 13th JCGC classified station No. 1 lymphadenectomy to the D2 level in patients with primary lower-third gastric cancer (LGC). This study was designed to re-evaluate the therapeutic value of lymphadenectomy, and to clarify the possible risk factors for station No. 1 lymph node metastasis (LNM) in LGC., Methods: Between 1997 and 2014, 1,875 consecutive patients with gastric cancer underwent curative gastrectomy with radical lymphadenectomy. Of these, 344 patients who had a tumor located in the lower (L) or lower-duodenum (LD) area were analyzed retrospectively., Results: 1) The therapeutic value of lymphadenectomy of stations No. 6, No. 3, No. 8a, No. 5, No. 4d, and No. 1 lymph nodes was proved to be higher than that of lymphadenectomy of other station lymph nodes. Patients with station No. 1 LNM had a significantly higher incidence of undifferentiated type, lymphatic invasion, venous invasion, and pT2-4 tumor. 2) Regarding factors to predict station No. 1 LNM in LGC, there was no station No. 1 LNM in patients with both early and differentiated type LGC. Distance from the pylorus to the tumor center (DPT) significantly correlated with station No. 1 LNM. Particularly, there was no station No. 1 LNM in patients with early LGC and DPT<50 mm., Conclusions: In patients with early and differentiated type LGC and DPT<50 mm, limited surgery to omit station No. 1 lymphadenectomy might be possible.

Wernicke's encephalopathy is usually related to alcoholism, malnutrition, or hyperemesis gravidarum. We report a case of Wernicke's encephalopathy after distal gastrectomy for gastric cancer. A 58-year-old man underwent distal gastrectomy with Billroth Ⅰreconstruction for early gastric cancer. Nine months later, he developed anorexia and vomiting for a few days. Brain MRI showed no significant findings, and he resumed ingestion 5 days after admission. On the 8th day of hospitalization, dysphagia suddenly developed and brain MRI indicated Wernicke's encephalopathy. Vitamin B1 was immediately injected, and neurological symptoms gradually improved. However, dysphagia did not adequately improve, leading to severe aspiration pneumonitis. Laparoscopic gastrostomy was performed for aspiration of the stomach contents and initiation of enteral nutrition. After gastrostomy, the patient made good progress and was transferred to a rehabilitation hospital. We should recognize that gastrectomy can cause Wernicke's encephalopathy.

Objective: Although the efficacy of adjuvant chemotherapy with oxaliplatin for colorectal cancer patients has been established, the tolerability of this regimen is rarely reported in Japan. The aim of this study was to clarify the tolerability of adjuvant oxaliplatin-based regimen for Japanese patients with colorectal cancer., Methods: This study included 158 advanced colorectal cancer patients who consecutively underwent a surgical procedure at our hospital and received adjuvant chemotherapy. Completion rate and adverse events were monitored in this study., Results: Among the 158 patients, 44 received oxaliplatin-based chemotherapy and the remaining received chemotherapy without oxaliplatin. The use of oxaliplatin was significantly correlated with more cases of adverse events such as myelosuppression (p<0.001) and peripheral neurotoxicity (p=0.005), which lead to dose reduction (p<0.001) or drug withdrawal (p<0.001). However, the completion rate did not significantly differ between the 2 groups. The median relative dose intensity (RDI) was 85.7%, which means that the oxaliplatin-based regimen is feasible. As for recurrence-free survival, no significant differences were observed between the 2 groups., Conclusion: This study demonstrates that adjuvant chemotherapy with oxaliplatin is tolerable by colorectal cancer patients in Japan.

A 67-year-old man was admitted to our hospital for treatment for multiple superficial esophageal cancers. Screening upper gastrointestinal endoscopy examination revealed a superficial squamous cell carcinoma (SCC) at the middle thoracic esophagus and Barrett's epithelium and a superficial adenocarcinoma at the abdominal esophagus. We performed a subtotal esophagectomy with gastric tube reconstruction via the retrosternal route. Pathological examination revealed a Barrett's adenocarcinoma at the abdominal esophagus. Esophageal cancer is thought to be a multicentric disease, and we sometimes find multiple esophageal cancers. In Japan, most cases of multiple esophageal cancers are composed of SCCs, and the occurrence of multiple esophageal cancers composed of SCC and Barrett's adenocarcinoma is rare. In contrast, the number of the patients with Barrett's esophagus is increasing, and the number of the patients with Barrett's adenocarcinoma also seems to be on the rise. Therefore, it is important be aware of the possibility of multiple esophageal cancers composed of SCC and Barrett's adenocarcinoma while making diagnoses.

Background: Thrombocytosis in patients with cancer is reportedly associated with an increased expression of angiogenic factors and a poor prognosis in some cancer types. The aim of this study was to analyze the clinicopathological significance and prognostic value of platelet counts in patients with gastric cancer., Methods: Preoperative platelet counts were measured in 306 patients with gastric cancer who underwent surgery between 2001 and 2010.We used the cut-off level of 250.9×10(3) mL (mean) to define thrombocytosis and then analyzed the correlation between platelet count and clinicopathological factors. The multivariate prognostic value was determined using the Cox proportional hazards model., Results: Platelet counts were significantly elevated in patients with lymph node metastasis (p=0.0349) and pStage Ⅲdisease (p=0.0326). Adjusting for venous invasion and pStage, multivariate analysis indicated that thrombocytosis as defined in this study was an independent prognostic factor (hazard ratio=1.50, 95%CI: 1.07-2.36, p=0.0402)., Conclusion: A high platelet count is associated with tumor progression and poor survival in patients with gastric cancer.

Background and Aims: The epidemiology of gastric cancer is changing with an increasing proportion of tumors in the upper stomach. This study was designed to identify risk factors and clinical problems related to the difference between clinical and pathological diagnosis of tumor depth in cases of upper third gastric cancer., Patients and Methods: A total of 119 consecutive patients with upper third gastric cancer, who underwent curative gastrectomy between 2008 and 2012, were retrospectively analyzed., Results: The patients were divided into 2 groups based on the pattern of the difference between the clinical (c) and pathological (p) diagnosis of the T factor. Thirty patients (25%) were included in the underestimated diagnosis group (UE group, cTpT or cT=pT). The number of cases showing undifferentiated type (TMN) and lymphatic invasion was significantly higher in the UE group compared to the OC group. Multivariate analysis revealed that the undifferentiated type (TMN) was an independent risk factor for underestimation (p<0.05)., Conclusion: The presence of undifferentiated components in upper third gastric cancer was associated with a high incidence of underestimated diagnosis. Care should be taken in decision-making for surgical treatments based on the clinical diagnosis.

Background: The association between intraoperative hemorrhage and the type of recurrence was examined, with a focus on peritoneal metastasis., Methods: A total of 540 patients who underwent macroscopically curative gastrectomy for advanced gastric cancers were reviewed for various clinicopathological characteristics, such as the amount of intraoperative hemorrhage and the pattern of recurrence. Additionally, adhesion assays using gastric cancer cells and mesothelial cells were performed in the presence of blood plasma to assess its effects on cell adhesion., Results: Large intraoperative hemorrhages were correlated with a higher risk of peritoneal metastasis, while small hemorrhages were not. However, there were no significant differences in the incidence of all recurrences or other types of recurrence between both groups. Multivariate analysis of all cases (T2-4) revealed that large intraoperative hemorrhages were not an independent risk factor for peritoneal recurrence (p = 0.144); however, the large hemorrhage group developed peritoneal recurrence more frequently than the small hemorrhage group in each T stage. In the adhesion assay, the ability of cancer cells and mesothelial cells to adhere to each other was enhanced by the addition of plasma to the culture medium. The addition of heparin significantly decreased the plasma-induced enhancement of cell adhesion of Kato III, but not MKN45 or MKN74., Conclusions: Advanced gastric cancer patients accompanied by a large amount of intraoperative hemorrhage are more likely to develop peritoneal recurrence, and this risk might be due, at least in part, to the increased ability of cancer cells and mesothelial cells to adhere to each other.

The nickel-mediated [3+2] cycloaddition of 2-trifluoromethyl-1-alkenes with alkynes afforded fluorine-containing multi-substituted cyclopentadienes in a regioselective manner. This reaction involves the consecutive two C-F bond cleavage of a trifluoromethyl or a pentafluoroethyl group through β-fluorine elimination., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Coagulation factor XIII( Fibrogammin P, F XIII) has been used to treat postoperative pancreatic fistulas following gastrectomy for gastric cancer in Japan. However, little is known about the best timing to start this treatment for early recovery. This study was designed to examine the appropriate time to start Fibrogammin P treatment for pancreatic fistulas, based on nutritional and inflammatory parameters., Method: We retrospectively examined 27 consecutive patients with Grade B or C pancreatic fistulas as defined by the International Study Group of Pancreatic Fistula( ISGPF) classification who underwent gastrectomy at our institute between 1997 and 2011. We analyzed data on total protein( TP), albumin (Alb), C-reactive protein( CRP), and hemoglobin( Hb) concentrations and white blood cell( WBC) and lymphocyte counts. We used this information to determine laboratory cut-off values that indicate the most advantageous time to start the administration of Fibrogammin P in order to achieve early recovery within 2 weeks., Result: When Fibrogammin P administration was based on more than 2 cut-off values such as Alb>2.6 g/dL and Hb>9.0 g/dL and WBC<9,000/μL (p= 0.1563), early cure of pancreatic fistulas was achieved., Conclusion: The use of nutritional and inflammatory parameter values to determine the best time to administer Fibrogammin P may shorten the treatment period.

Background: We examined the levels of long non-coding RNAs (lncRNAs) in the plasma of patients with gastric cancer to assess their clinical significance for diseases diagnosing and monitoring., Materials and Methods: We investigated the stability of plasma lncRNAs, and then confirmed the appropriateness of the lncRNA assay with a pre-amplification method. The levels of plasma lncRNAs, H19, HOX antisense intergenic RNA (HOTAIR), and metastasis associated lung adenocarcinoma transcript-1 (MALAT1), were then analyzed in patients with gastric cancer (GC) and healthy controls., Results: Plasma lncRNAs exhibited minimal gradual instability only under several severe conditions. Analysis showed that samples with pre-amplification had a higher level of linearity in the reverse transcription polymerase chain reaction (RT-PCR) assay than those without pre-amplification. Plasma H19 levels were significantly higher in patients than in healthy controls. Plasma H19 levels were significantly reduced in postoperative samples., Conclusion: Circulating lncRNAs can be detectable in plasma, and the detection of circulating lncRNAs may provide new complementary tumor markers for gastric cancer.

Background: MicroRNAs (miRNAs) such as miR-17-5p, miR-21, miR-106a and miR-106b are reported to be highly expressed in gastric carcinoma (GC) tissues. Recently, we reported that these miRNAs were consistently detectable in plasma and reflected tumor dynamics of GC. We hypothesized that these plasma miRNA concentrations could be used as prognostic markers in patients with GC., Materials and Methods: Between 2008 and 2009, preoperative plasma samples were collected from 69 consecutive patients with GC at our hospital. We retrospectively examined the association between plasma miRNA concentrations and prognosis., Results: The postoperative cause-specific survival rate of patients with high plasma miR-21 concentration was significantly poorer than those with a low concentration (p=0.0451), as was that of those with high plasma concentration of miR-106a (p=0.1132). There were no prognostic differences according to the plasma concentration of miR-17-5p and miR-106b. Those with high miR-21 concentration had also a slightly higher incidence of vascular invasion (p=0.0311). Multivariate analysis revealed that the presence of a high miR-21 concentration in plasma was an independent prognostic factor (p=0.0133, hazard ratio: 13.4 (95% CI: 1.72-104.4))., Conclusion: The level of circulating miR-21 could be a reliable prognostic marker in the plasma of patients with GC. These findings contribute to the stratification of patients in order to identify those who need meticulous follow-up for early detection of recurrence and additional or alternative treatments of GC.

Background: miR-21 and miR-375 are reported to be highly and poorly expressed in esophageal squamous cell carcinoma (ESCC) tissues, respectively. Recently, we demonstrated that circulating miR-21 and miR-375 were stably detectable in plasma and reflected tumor dynamics as a tumor marker for ESCC. We hypothesized that these plasma miRNA concentrations contributed to prognostic markers in patients with ESCC., Methods: Between 2008 and 2010, 50 preoperative plasma samples were collected from consecutive patients with ESCC, who underwent curative esophagectomy in our hospital. We examined the association between plasma miRNA concentrations and prognosis retrospectively., Results: i) The postoperative cause-specific survival rate of patients with high plasma miR-21 concentration tended to be poorer than low group (3-yr survival rate: 53.4 and 81.5%, p = 0.1038), while that of high plasma miR-375 group was better than low group (3-yr survival rate: 100 and 65.2%). ii) Patients with high miR-21 and low miR-375 concentrations in plasma had significantly poorer prognosis than other patients (3-yr survival rate: 48.4 and 83.1%, p = 0.039). Multivariate analysis revealed that the presence of high miR-21 and low miR-375 concentrations in plasma was an independent prognostic factor (p = 0.029, hazard ratio 3.8 (1.14-12.5))., Conclusion: Circulating miR-21 and miR-375 could be reliable prognostic markers for ESCC. These plasma markers might facilitate clinical decision-making to select prospective candidates, which need meticulous follow-up for early detection of recurrences and additional treatments such as neo-adjuvant chemotherapy and postoperative chemotherapy in ESCC.

We performed a subtotal esophagectomy with gastric tube reconstruction by hand assisted laparoscopic surgery and laparoscopic sigmoidectomy simultaneously for the patient with middle thoracic esophageal cancer and lateral spreading tumor in the sigmoid colon. Upper abdominal and transumbilical incisions were made and Lap Discs (regular, mini) were set respectively. Two 12 mm ports were inserted in the right flank and lower quadrant, and two 5 mm ports were inserted in the left flank and lower quadrant. First, by using video-scope from upper Lap Disc, laparoscopic sigmoidectomy was performed. Anastomosis was performed via lower Lap Disc. For the gastric tube reconstruction, upper Lap Disc was used for hand assistance, and video-scope was inserted from lower Lap Disc. The patient was discharged at 26 days after surgery without complications. In conclusion, our surgical procedure provided a good surgical view and decreased a surgical stress.