Preoperative MRI for predicting pathological changes associated with surgical difficulty during laparoscopic cholecystectomy for acute cholecystitis.

BACKGROUND: Severe inflammation with necrosis and fibrosis of the gallbladder in acute cholecystitis increases operative difficulty during laparoscopic cholecystectomy. This study aimed to assess the use of preoperative MRI in predicting pathological changes of the gallbladder associated with surgical difficulty. METHODS: Patients who underwent both preoperative MRI and early cholecystectomy for acute cholecystitis between 2012 and 2018 were identified retrospectively. On the basis of the layered pattern of the gallbladder wall on MRI, patients were classified into three groups: high signal intensity (HSI), intermediate signal intensity (ISI), and low signal intensity (LSI). The endpoint was the presence of pathological changes of the gallbladder associated with surgical difficulty, such as necrosis, abscess formation and fibrosis. RESULTS: Of 229 eligible patients, pathological changes associated with surgical difficulty were found in 17 (27 per cent) of 62 patients in the HSI group, 84 (85 per cent) of 99 patients in the ISI group, and 66 (97 per cent) of 68 patients in the LSI group (P < 0·001). For detecting these changes, intermediate to low signal intensity of the gallbladder wall had a sensitivity of 90 (95 per cent c.i. 84 to 94) per cent, specificity of 73 (60 to 83) per cent and accuracy of 85 (80 to 90) per cent. CONCLUSION: Preoperative MRI predicted pathological changes associated with surgical difficulty during laparoscopic cholecystectomy for acute cholecystitis.

ANTECEDENTES: La inflamación grave con necrosis y fibrosis de la vesícula biliar en la colecistitis aguda aumenta la dificultad quirúrgica durante la colecistectomía laparoscópica. Este estudio tuvo como objetivo evaluar el uso de la resonancia magnética preoperatoria (magnetic resonance imaging, MRI) para predecir los cambios patológicos de la vesícula biliar asociados con la dificultad quirúrgica. MÉTODOS: Los pacientes que se sometieron tanto a MRI preoperatoria como a colecistectomía precoz por colecistitis aguda entre 2012 y 2018 fueron identificados retrospectivamente. En base a la distribución en capas de la pared de la vesícula biliar en la MRI, los pacientes se clasificaron en tres grupos: (1) intensidad de señal alta (high signal intensity, HSI), (2) intensidad de señal intermedia (intermediate signal intensity, ISI) y (3) intensidad de señal baja (low signal intensity, LSI). El objetivo final fue la presencia de cambios patológicos en la vesícula biliar asociados con la dificultad quirúrgica, tales como necrosis, formación de abscesos y fibrosis. RESULTADOS: De los 229 pacientes elegibles, se documentaron cambios patológicos asociados con dificultad quirúrgica en 17 (27,4%) de 62 pacientes en el grupo HSI, 84 (84,8%) de 99 pacientes en el grupo ISI y 66 (97,1%) de 68 pacientes en el grupo LSI (P < 0,001). Para detectar estos cambios, la intensidad de señal de intermedia a baja de la pared de la vesícula biliar tuvo una sensibilidad del 89,8% (i.c. del 95% 84,2%-94,0%), una especificidad del 72.6% (i.c. del 95% 59,8%-83,1%) y una precisión del 85,2% (i.c. del 95% 79,9%-89,5%). CONCLUSIÓN: La MRI preoperatoria predijo los cambios patológicos asociados con la dificultad quirúrgica durante la colecistectomía laparoscópica por colecistitis aguda.

Randomized clinical trial of single skin sterilization with a povidone-iodine applicator versus conventional skin sterilization in abdominal surgery.

Background: The efficacy of widely used povidone-iodine applicators for skin sterilization in abdominal surgery is unclear. The aim of this trial was to evaluate whether sterilization with a povidone-iodine applicator was not inferior to a conventional sterilization method. Methods: Patients undergoing elective abdominal surgery were assigned randomly to receive single sterilization with the applicator or conventional sterilization. The primary endpoint was wound infection rate. Secondary endpoints were rate of organ/space surgical-site infection (SSI), adverse effects of povidone-iodine, amount of povidone-iodine used and total cost of sterilization. Results: Of 498 patients eligible for the study between April 2015 and September 2017, 240 were assigned and analysed in the applicator group and 246 in the conventional group. Wound infection was detected in 16 patients (6·7 per cent) in the applicator group and 16 (6·5 per cent) in the conventional group (absolute difference 0·0016 (90 per cent c.i. -0·037 to 0·040) per cent; P = 0·014 for non-inferiority). There was no difference between the groups in the organ/space SSI rate (11 patients (4·6 per cent) in the applicator group and 16 (6·5 per cent) in the conventional group. Both the amount of povidone-iodine used and the total cost of sterilization were higher in the conventional group than in the applicator group (median 76·7 versus 25 ml respectively, P < 0·001; median €7·0 versus €6·4, P < 0·001). Skin irritation was detected in three patients in the conventional group. Conclusion: In abdominal surgery, this povidone-iodine applicator was not inferior to conventional sterilization in terms of the wound infection rate, and it is cheaper. Registration number: UMIN000018231 (http://www.umin.ac.jp/ctr/).

Comparison between dexmedetomidine and midazolam as a sedation agent with local anesthesia in inguinal hernia repair: randomized controlled trial.

PURPOSE: In Japan, inguinal hernia repair is widely performed with local anesthesia. The objective of this study was to evaluate safety and efficacy of intravenous dexmedetomidine as a sedation agent with local anesthesia in inguinal hernia repair. METHODS: We performed this randomized, single-blind study for 200 patients who were scheduled to undergo inguinal hernia repair with local anesthesia. Patients were randomly divided into two groups (dexmedetomidine group: Group D, midazolam group: Group M). The primary outcome was to evaluate the safety of intravenous dexmedetomidine. Secondary outcomes were to analyze results of operators' surveys and patients' questionnaires and evaluate implementation of conscious sedation. RESULTS: Incidence of respiratory depression was significantly higher in Group M than Group D (p = 0.03). Other adverse events examined did not differ significantly. All three operators' questionnaires indicated that results were better in Group D than Group M. More than 70% of patients in both groups were satisfied with the surgery. More than 80% of Group D patients and 74% of Group M patients achieved a state of conscious sedation. CONCLUSION: This study demonstrated that intravenous dexmedetomidine during hernia repair with local anesthesia is safe and the results were satisfactory to both operators and patients.

Global histone modification of H3K27 correlates with the outcomes in patients with metachronous liver metastasis of colorectal cancer.

BACKGROUND: We evaluated the methylation patterns of histone H3 lysine 27 (H3K27), H3 lysine 36 (H3K36) and the expression of H3K27 methylase EZH2 in patients with colorectal carcinomas with metachronous liver metastasis to search for biomarkers identifying these patients. METHODS: Double 2-mm core tissue microarrays were made from 54 paraffin-embedded samples of primary colorectal adenocarcinomas and corresponding liver metastases and examined using an immunohistochemical analysis of dimethylation and trimethylation in H3K27, H3K36 and EZH2. Positive tumor cell staining for each histone modification (H-score) was used to classify patients into low- and high-staining groups, which were then examined to identify any correlations between the clinicopathological parameters and the clinical outcomes. RESULTS: The H-scores of H3K27me2 were lower in the liver metastases than in the corresponding primary tumors, while the H-scores of H3K36me2 were higher in the liver metastases than in the corresponding primary tumors (P < 0.001). H3K27me2 in the primary tumors correlated with tumor size (P = 0.016), H3K36me2 in the primary tumors correlated with histological type (P = 0.038), and H3K36me3 in the primary tumors correlated with lymph node metastasis (P = 0.017). In addition, lower levels of H3K27me2 in the primary tumors correlated with poorer survival rates (P = 0.039). The multivariate survival analysis showed that the H3K27me2 status is an independent prognostic factor for colorectal cancer patients (P = 0.047). CONCLUSIONS: Our findings suggest that the methylation level of H3K27me2 detected with immunohistochemistry may be an independent prognostic factor for metachronous liver metastasis of colorectal carcinomas.

Synchronous and subsequent lesions of serrated adenomas and tubular adenomas of the colorectum.

The characteristics of synchronous and subsequent lesions of serrated adenomas (SAs) of the colorectum are still unclear. This study aimed to clarify the characteristics of synchronous and subsequent lesions of SAs compared with tubular adenomas (TAs) of the colorectum. Patients were divided into 2 groups: SA (127 patients) and TA (158 patients). The mean follow-up durations in the SA and TA groups were 39.7 and 42.7 months, respectively. The number and clinical features of the synchronous and subsequent lesions of both groups were examined. In the SA group, 19 (15%) patients had synchronous lesions and 3 (2%) patients had subsequent lesions. In the TA group, 68 (43%) patients had synchronous lesions and 14 (9%) patients had subsequent lesions. The frequencies of patients with synchronous and subsequent lesions in the SA group were significantly lower than those in the TA group (p < 0.0001 and p = 0.02, respectively). The most frequent synchronous lesion was SA (67%) in the SA group and TA (95%) in the TA group. The most subsequent lesion was SA (62%) in the SA group and TA (100%) in the TA group. The histology of the index polyp and synchronous and subsequent lesions tended to be identical. No invasive colorectal carcinomas were observed in either group. Our data suggest that the colonic tumorigenesis potential of patients with SA may differ from that of patients with TA.

Metachronous multiple esophageal squamous cell carcinomas and Lugol-voiding lesions after endoscopic mucosal resection.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection (EMR) has been applied to the treatment of superficial esophageal squamous cell carcinoma (SCC). The incidence and characteristics of metachronous multiple esophageal SCCs and Lugol-voiding lesions (LVLs) were investigated in a retrospective study in patients who had undergone EMR for superficial esophageal SCC. PATIENTS AND METHODS: 96 patients with esophageal SCC who had been treated by EMR were followed up by endoscopy for 12 months or longer. Clinicopathologic parameters such as tumor size and location and presence of LVLs were examined. RESULTS: 10 patients (10 %) had synchronous multiple SCCs, and 12 (13 %) developed metachronous multiple SCCs. The mean annual incidence of newly diagnosed tumor was 4.4 %. The incidence of a speckled pattern of LVLs was 20/74 (27 %) in patients with solitary SCC, 5/10 (50 %) in synchronous multiple SCC, and 10/12 (83 %) in metachronous multiple SCC. The incidence of the presence of speckled pattern of LVLs was significantly higher in patients with multiple SCCs than in those with solitary SCC (68 % vs. 27 %, P = 0.0004). CONCLUSIONS: Patients who have undergone EMR for esophageal SCC, especially those with metachronous multiple LVLs in the background mucosa, should undergo follow-up with close endoscopic observation using Lugol staining.

Emergence of complex rearrangements at translocation breakpoints in a transgenic mouse; implications for mechanisms involved in the formation of chromosome rearrangements.

Cryptic complex rearrangements as a result of a reciprocal chromosome translocation have been characterised in a transgenic mouse strain. Analysis of the breakpoint junctions in our previous studies showed that the ada transgene was integrated at the breakpoint forming a fusion gene with Golga3 (Mea2). In this study, further detailed analysis around the translocation junctions revealed that the surrounding regions were composed of 13 fragments of defined transgenic chromosome origins over approximately 1.9-Mb areas. Exactly the same cluster structure of these 13 breakpoint fragments already existed in the second generation of the transgenic mice. Our results show that this highly complex rearrangement has been conserved as the incipient form without any additional changes for 18 years up to the present generation, suggesting simultaneous occurrence of multiple events in the founder mouse.

Helicobacter pylori-associated gastritis is related to babA2 expression without heterogeneity of the 3' region of the cagA genotype in gastric biopsy specimens.

BACKGROUND: Cytotoxin-associated gene A (cagA) is the major virulence factor of Helicobacter pylori strains and affects the clinical outcome of patients. Blood group antigen binding adhesin (BabA) helps the strains adhere to the epithelial cell layer and is the most important adhesin of H. pylori. OBJECTIVES: We tried to study the association between the status of babA2 and cagA in H. pylori strains and histological gastritis. methods: Thirty-six patients were included. RNA was extracted from two frozen biopsy samples of the antrum and corpus, respectively, and cagA/babA2 genotypes were analyzed with reverse transcription polymerase chain reaction and direct sequencing. Two gastric specimens of the antrum and corpus, respectively, were also stained with hematoxylin and eosin to analyze H. pylori-related gastritis. RESULTS: In the antrum, 56% of the specimens were babA2 positive and in the corpus 53%. The gastritis scores of activity and inflammation were associated with the presence of babA2 in antrum specimens but not in corpus specimens. cagA gene encoding in the CagA EPIYA-D region was detected in all samples, and the sequence was completely identical between those from the gastric corpus and antrum. CONCLUSION: babA2 expression is heterogeneous and correlated with the extent of gastritis in the antrum, but not in the corpus, whereas cagA shows a monotonous genotype.

Endoscopic submucosal dissection for residual/local recurrence of early gastric cancer after endoscopic mucosal resection.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection (EMR) is a widely accepted treatment for early gastric cancer; however, incomplete resection with residual local disease and recurrences continues to be a difficult problem. The aim of this study was to evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for residual/local recurrent early gastric cancer lesions after EMR. PATIENTS AND METHODS: The en bloc resection rate, histologically complete resection rate, complications, and local recurrence were assessed in 15 patients who underwent ESD for residual/local recurrent early gastric cancer lesions after EMR. RESULTS: The nonlifting sign after injection of a glycerin solution was positive due to scar formation in all cases. En bloc resection was attempted in all cases, with a complete resection rate of 93.3 % (14 of 15). The lesion was completely resected with histologically adequate margins in the 14 patients who received complete en bloc resection. The average operation time was 85.4 +/- 52.9 min, and the mean follow-up period for all patients was 18.1 +/- 7.4 months. Major bleeding during the procedure in one case was the only complication (one of 15, 6.7 %). None of the patients experienced recurrence of early gastric cancer after ESD. CONCLUSIONS: ESD appears to be a safe and effective treatment for residual/local recurrent early gastric cancer lesions after EMR, and it is useful for histological confirmation of successful treatment.

Novel heteroduplex method using small cytology specimens with a remarkably high success rate for analysing EGFR gene mutations with a significant correlation to gefitinib efficacy in non-small-cell lung cancer.

We conducted a feasibility study to examine whether small numbers of cancer cells could be utilised for analysis of the EGFR gene status using the loop-hybrid mobility shift assay, which is a modified heteroduplex technique. Cytology specimens obtained by transbronchial abrasion were successfully used for analysis of the EGFR gene status in 50 of 52 (96.2%) patients diagnosed with class V non-small-cell carcinoma. Furthermore, the relationship between the EGFR gene status and clinical outcome was analysed in 25 patients treated with gefitinib. Overall, 10 of 11 patients with EGFR mutations in exon 19 or 21 showed tumour regression with gefitinib treatment, compared to only two of 14 patients with wild-type EGFR. The response rate was significantly higher in the EGFR mutation group than in the wild-type EGFR group (90.9 vs 14.3%, P=0.00014). Logistic regression analysis revealed that EGFR mutations in cytology specimens represented an independent predictor of the gefitinib response. The overall and progression-free survivals were significantly longer in the EGFR mutation group than in the wild-type EGFR group (P<0.05). In conclusion, cytology specimens could be useful for analysing the EGFR status in the majority of patients with non-small-cell lung cancer to determine whether they are likely to benefit from gefitinib treatment.

Nuclear and mitochondrial DNA microsatellite instability in gastrointestinal stromal tumors.

OBJECTIVE: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. Nuclear (nMSI) and mitochondrial microsatellite instability (mtMSI) play important roles in tumorigenesis in various organs. The aim of this study was to evaluate the role of nMSI and mtMSI in GISTs. METHODS: Samples from 74 mesenchymal tumors were collected. nMSI and mtMSI were examined by microsatellite assay at BAT26 and D310 mononucleotide repeats in mtDNA, respectively. We compared nMSI, mtMSI and clinicopathologic features, including patient age and sex, tumor location, tumor size, presence of tumor ulceration and presence of distant metastasis, for 51 GISTs for which these data were available. RESULTS: nMSI and mtMSI were detected in 3 (5%) and 10 (16%) of the 62 GISTs, respectively. There was no significant relationship between nMSI, mtMSI and clinicopathologic features. CONCLUSION: These results suggest that mtMSI may play a role, but that nMSI may play little role in the development of GISTs.

Loss of heterozygosity on chromosome 10p14-p15 in colorectal carcinoma.

High frequencies of loss of heterozygosity (LOH) on chromosome 10p14-p15 have been reported in various tumors, including gliomas, pulmonary carcinoid tumors and cervical, hepatic, prostatic and esophageal carcinomas. However, LOH on chromosome 10p14-p15 in colorectal tumors has not been reported. Therefore, we examined LOH on chromosome 10p14-p15 in 60 colorectal carcinomas (21 superficial and 39 advanced types) by microsatellite assay. Three microsatellite loci, D10S191 (10p14), D10S558 and D10S249 (10p15) were examined by polymerase chain reaction [early colorectal carcinomas, LOH of markers D10S191 (36%), D10S558 (7%) and D10S249 (11%), and in advanced colorectal carcinomas, LOH of markers D10S191 (20%), D10S558 (13%) and D10S249 (33%)]. There were no significant associations between LOH on chromosome 10p14-p15 and clinicopathologic features, including patient age, sex, tumor location, depth of invasion, histologic type, lymph node metastasis and prognosis. These data suggest that a putative tumor suppressor gene associated with colorectal carcinogenesis may be located on chromosome 10p14-p15 and that alteration of this gene may be involved in the development but not progression of colorectal tumors.

Morphological changes in human gastric tumours after eradication therapy of Helicobacter pylori in a short-term follow-up.

BACKGROUND: It is controversial as to whether the development of gastric cancer is influenced by Helicobacter pylori eradication. If eradication itself influences the tumour morphology, this may affect the tumour discovery rate. AIM: To investigate the morphological changes in the gastric neoplasm after H. pylori eradication. METHODS: We studied 37 patients with eradication therapy. After a 1-month follow-up, endoscopic re-evaluation was performed and the appearance was compared with first image. All lesions were resected endoscopically, and were subjected to histological assessment and to immunohistochemistry. Serum gastrin levels were determined before and after eradication. RESULTS: Twenty-nine of 37 patients underwent successful eradication. The appearance of 11 lesions (33% of 33 lesions) became indistinct after successful eradication. All lesions were of the superficial-elevated type and the height of the lesions decreased. We detected normal columnar epithelium over the neoplasm in eight of the lesions. Higher expression of single-stranded deoxyribonucleic acid in the deep area was characteristic in tumours with an indistinct appearance. These changes did not correlate with the serum gastrin levels. CONCLUSIONS: The morphology of the gastric neoplasm change after eradication in the short-term. This may contribute to the decreased tumour discovery rate.

Diagnostic ability of high-frequency ultrasound probe sonography in staging early gastric cancer, especially for submucosal invasion.

BACKGROUND: Advances in gastrointestinal endoscopy have resulted in endoscopic mucosal resection becoming the main therapy for many early gastric cancers confined to the mucosa and, in some cases, of minimal submucosal invasion. Thus, preoperative determination of the depth of the cancer is important. We compared the results of high-frequency ultrasound probe sonography with those of histologic study to clarify the usefulness of identifying of submucosal invasion and determining the depth of early gastric cancer. METHODS: Subjects were 295 patients diagnosed with early gastric cancer who had undergone endoscopic mucosal or surgical resection. High-frequency ultrasound probe sonographic findings were compared with histologic findings. RESULTS: The muscularis mucosae was visualized in 63% of cases of early gastric cancer. By construction on receiver operator characteristics curve, we determined that submucosal invasive cancer could be diagnosed by high-frequency ultrasound probe sonography to a depth of about 600 microm. There was no case in which invasion deeper than 1000 microm was diagnosed as a hypoechoic area limited to the mucosal layer or a fan-shaped hypoechoic area in the submucosal layer. The depth of early gastric cancer was accurately determined in 90% of cases. CONCLUSIONS: High-frequency ultrasound probe is a useful tool for accurately determining the depth of invasion of early gastric cancer when its limitations are understood.

Magnifying gastroendoscopy for diagnosis of histologic gastritis in the gastric antrum.

BACKGROUND: We investigated the potential of magnifying endoscopy for diagnosis of histologic gastritis in the gastric antrum. In addition, we investigated whether magnifying endoscopy can be applied for evaluation of Helicobacter pylori eradication therapy. METHODS: We examined 176 Japanese patients including 53 with H. pylori eradication. We evaluated the antrum by magnifying observation and ordinary endoscopic findings, and compared these results. Biopsy specimens were taken from the sites observed. RESULTS: The magnified views were classified into four types. Histology of the biopsy specimens allowed us to match the four magnified views with normal mucosa with fundic glands, normal mucosa with pyloric glands, mucosa with gastritis and intestinal metaplasia/epithelial hyperplasia. The types of magnifying appearances were specific enough for the diagnosis of histologic gastritis (148 out of the 176 (82.4%) cases; sensitivity, 96.3%; specificity, 73.7%). We could accurately diagnose the histologic gastritis by magnifying endoscopy in 49 out of the 53 (92%) cases with H. pylori eradication, while only in 38% by ordinary endoscopy. The accuracy of diagnosis was statistically higher with the use of magnifying endoscopy than with ordinary endoscope (P < 0.001). CONCLUSION: Magnifying gastroendoscopy is useful to judge the histologic gastritis, especially, in cases with H. pylori eradication.

Characteristics and trends of clarithromycin-resistant Helicobacter pylori isolates in Japan over a decade.

Clarithromycin has been administered to patients in Japan since 1991. Clarithromycin-resistant Helicobacter pylori strains have been on the rise in Japan. We obtained H. pylori isolates between 1989 and 2000 and examined mutations of the 23S rRNA gene, which are closely associated with clarithromycin resistance. Isolates were obtained from 356 patients with H. pylori infection treated at the Hiroshima University. Sixty-one of the patients received clarithromycin-based H. pylori eradication therapy. Mutations of the 23S rRNA gene were examined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) followed by sequencing analysis. Mutant strains were found in 42 of the 356 patients (11.8%). The prevalence of mutant strains increased from 0 to 20.4% during the 12-year study period. The prevalence increased to more than 10% by 1995 and then to more 20% after 1999. The H. pylori eradication rate was significantly higher in patients with wild-type strains than in patients with mutant strains (72.0 vs. 36.4%, p = 0.024). Our data indicate that clarithromycin-resistant H. pylori strains have increased rapidly since 1995 and that the effectiveness of clarithromycin-based H. pylori eradication therapies may soon be compromised. Other new therapies may be necessary as first-line treatments in Japan.

Necessity of multiple gastric biopsies from different sites for detection of clarithromycin-resistant Helicobacter pylori strains.

BACKGROUND: It has been reported that approximately 10% of patients infected with Helicobacter pylori have both clarithromycin-susceptible and clathromycin-resistant strains. However, there have been no reports indicating whether only one gastric biopsy is sufficient to detect clarithromycin-resistant strains. METHODS: Sixty-five H. pylori-infected patients were selected for this study, and 40 of them were given clarithromycin-based eradication therapy. Four gastric biopsies, 2 from the antrum and 2 from the corpus, were obtained from each of the 65 patients. Susceptibility of H. pylori strains to clarithromycin was examined by detecting mutations of the 23S ribosomal RNA (rRNA) gene of H. pylori. RESULTS: The clarithromycin-resistant strains were detected in 16 of the 65 (25%) patients. Only 5 of the 16 (31%) patients had the resistant strains in both the antrum and corpus. When only 1 or the other biopsy from the antrum was used, the resistant strains were detected in 8 (50%) or 9 (56%) of the 16 patients. CONCLUSIONS: These data indicate that multiple gastric biopsies from both the antrum and the corpus should be used to detect clarithromycin-resistant H. pylori strains.