[A Case of Resected Type 4 Rectal Cancer with Difficulty in Preoperative Diagnosis].

We reported a case of Type 4 rectal cancer performed laparoscopic surgery. A 73-year-old man had diarrhea and constipation and underwent colonoscopy. From the first colonoscopy, histological findings of biopsy showed non-neoplastic cells. The results of colonoscopy strongly suggested the possibility of Type 4 rectal cancer. Therefore, we performed colonoscopy twice and he was diagnosed Type 4 rectal cancer. Computed tomography revealed no distant metastasis. He underwent radical laparoscopic surgery. The histopathological diagnosis was pStage Ⅲc(The 9th edition). He then received adjuvant chemotherapy but was relapsed at bones and lymph nodes. He died 18 months later after surgery.

Pancreatic juice cytology as sensitive test for detecting pancreatic malignancy in intraductal papillary mucinous neoplasm of the pancreas without mural nodule.

OBJECTIVE: Recent studies reported that mural nodule (MN) was the most associated with malignant intraductal papillary mucinous neoplasms (IPMNs). However, IPMNs without MN cannot be diagnosed as malignant if only MN is determined to be indicator of malignancy. This study aimed to investigate role of pancreatic juice cytology for IPMNs without MN. METHODS: Medical records of 50 patients with histologically proven malignant IPMNs were reviewed. Exclusively for non-invasive cancer, extent of high-grade dysplasia along the main pancreatic duct (MPD) was determined microscopically. RESULTS: Thirty-six percent IPMNs had no MN. Cyst and main MPD diameter were significantly smaller in IPMN without MN compared to those in IPMN with MN (23 ± 14.1 vs 35 ± 13.2 mm, p = 0.010; 6.6 ± 4.3 vs 10.9 ± 6.1 mm, p = 0.006). Sensitivity of pancreatic juice cytology was higher in IPMN without MN compared to that in IPMN with MN (94% vs 53%, p = 0.004) although it could be affected by selection bias of study patients. Absence of MN was determined to be an independent factor associated with true positive cytology (OR = 24.3, p = 0.005). Extent of high-grade dysplasia was significantly longer in IPMN with true positive cytology compared to that in IPMN with false negative cytology (46.8 ± 20.5 vs 26.4 ± 11.0 mm, p = 0.005), and tended to be longer in IPMN without MN compared to that in IPMN with MN (47.0 ± 19.0 vs 36.0 ± 20.1 mm, p = 0.16). CONCLUSIONS: Sensitivity of pancreatic juice cytology was excellent in IPMN without MN. Pancreatic juice cytology may be a sensitive test for detection of pancreatic malignancy in IPMN without MN compared to high-risk imaging features.

Elastography for the pancreas: Current status and future perspective.

Elastography for the pancreas can be performed by either ultrasound or endoscopic ultrasound (EUS). There are two types of pancreatic elastographies based on different principles, which are strain elastography and shear wave elastography. The stiffness of tissue is estimated by measuring the grade of strain generated by external pressure in the former, whereas it is estimated by measuring propagation speed of shear wave, the transverse wave, generated by acoustic radiation impulse (ARFI) in the latter. Strain elastography is difficult to perform when the probe, the pancreas and the aorta are not located in line. Accordingly, a fine elastogram can be easily obtained in the pancreatic body but not in the pancreatic head and tail. In contrast, shear wave elastography can be easily performed in the entire pancreas because ARFI can be emitted to wherever desired. However, shear wave elastography cannot be performed by EUS to date. Recently, clinical guidelines for elastography specialized in the pancreas were published from Japanese Society of Medical Ultrasonics. The guidelines show us technical knacks of performing elastography for the pancreas.

Mural nodule of 10 mm or larger as predictor of malignancy for intraductal papillary mucinous neoplasm of the pancreas: Pathological and radiological evaluations.

BACKGROUND: We had previously reported that mural nodule (MN) ≥10 mm was optimal predictor of malignancy for intraductal papillary mucinous neoplasm (IPMN). However, little is known about its microscopic findings and imaging detectability. METHODS: Medical records and resected specimens of consecutive patients with IPMNs harboring MN ≥ 10 mm were reviewed. Imaging detectability was determined on reports basis. Malignant IPMNs (noninvasive + invasive carcinomas) were microscopically classified according to localization of high-grade dysplasia (HGD) within MN. RESULTS: Thirty-six patients were included. Imaging detectability of MN ≥ 10 mm in CT, MRI, US and EUS were 64%, 68%, 89%, and 97%, respectively. Thirty-three (92%) IPMNs were histologically diagnosed as malignant. Thirty percent of malignant IPMNs were classified into "diffuse HGD within MN", 40% into "focal HGD within MN", and 30% into "HGD outside MN", in which HGD was not located within MN but in low papillary epithelia around MN. Overall sensitivity of pancreatic juice cytology was calculated as 58%, and for "diffuse HGD within MN", "focal HGD within MN", and "HGD outside MN" as 80%, 62%, and 30%, respectively (p = 0.0237). Univariate-analysis showed localization of HGD within MN was associated with true positive cytology (OR = 5.33, p = 0.043). CONCLUSIONS: Detectability of MN ≥ 10 mm is excellent in US and EUS. Although HGD is observed within MN in 70% of malignant IPMNs, HGD is located only in low papillary epithelia around MN in the remaining 30%, in which sensitivity of pancreatic juice cytology is shown to be inadequate.

JSUM ultrasound elastography practice guidelines: pancreas.

Ultrasound elastography is a relatively new diagnostic technique for measuring the elasticity (hardness) of tissue. Eleven years have passed since the debut of elastography. Various elastography devices are currently being marketed by manufacturers under different names. Pancreatic elastography can be used not only with transabdominal ultrasonography but also with endoscopic ultrasonography, but some types of elastography are difficult to perform for the pancreas. These guidelines aim to classify the various types of elastography into two major categories depending on the differences in the physical quantity (strain, shear wave), and to present the evidence for pancreatic elastography and how to use pancreatic elastography in the present day. But the number of reports on ultrasound elastography for the pancreas is still small, and there are no reports on some elastography devices for the pancreas. Therefore, these guidelines do not recommend methods of imaging and analysis by elastography device.

Imaging morphological changes of intraductal papillary mucinous neoplasm of the pancreas was associated with its malignant transformation but not with development of pancreatic ductal adenocarcinoma.

BACKGROUND/OBJECTIVE: A considerable number of branch duct intraductal papillary mucinous neoplasm (BD-IPMN) developed not infrequently pancreatic malignancy, either as part of IPMN (malignant IPMN) or as concomitant pancreatic ductal adenocarcinoma (PDAC). To date, imaging morphological changes predicting occurrence of malignancy in BD-IPMN are not well-investigated. This study aimed to evaluate the relationships between occurrence of malignancy in BD-IPMN and imaging morphological changes of the tumors observed during follow-up. METHODS: 515 BD-IPMN patients with mural nodule <10 mm and negative cytology were included. 19 patients developed malignant IPMN and 8 patients developed concomitant PDAC during mean follow-up of 4.7 years. The following imaging morphological features were assessed: cyst/main pancreatic duct (MPD) diameter, occurrence of additional cyst/mural nodule. RESULTS: Growth rate of cyst/MPD diameter were significantly larger in patients who developed malignant IPMN compared to those in patients whose IPMN remained benign (p = 0.013, p = 0.01). Occurrence of additional cyst/mural nodule were more frequently observed in patients who developed malignant IPMN (p = 0.009, p = 0.04). In contrast, none of the factors associated with imaging morphological changes of IPMN were shown to be significantly different between patients who developed concomitant PDAC and patients whose IPMN remained benign. Growth rate of MPD diameter and occurrence of additional cyst were independent factors associated with development of malignant IPMN (odds ratio 21.5, and 5.62, respectively). CONCLUSIONS: Imaging morphological changes of IPMN, such as growth rate of MPD diameter and occurrence of additional cyst, could be indicators for development of malignant IPMN, but not for development of concomitant PDAC.

Usefulness of dual-phase 18F-FDG PET/CT for diagnosing small pancreatic tumors.

OBJECTIVES: The usefulness of dual-phase F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) for pancreatic tumors was investigated including numerous small tumors. METHODS: Consecutive 116 patients with solid pancreatic tumors were subjected. Maximum standard uptake values (SUVmax) at 1 and 2 hours after FDG injection were defined as early and delayed SUVmax, respectively. Receiver operating characteristic curve was used to determine the optimal cutoff value of early SUVmax. Diagnostic accuracy of dual-phase FDG PET/CT was compared with that of single phase. RESULTS: The mean ± SD tumor size was 25 ±12 mm in diameter. The level of early SUVmax and proportion of elevated SUVmax in delayed phase were significantly higher in malignancy than those in benignancy for less than 25 mm tumors (4.1 ± 2.6 vs 1.9 ± 0.5, P < 0.001; 89% vs 17%, P < 0.0001) although they did not reach statistical significance for greater than or equal to 25 mm tumors. When diagnostic criteria of dual-phase FDG PET/CT for less than 25 mm tumors were determined as (1) early SUVmax greater than or equal to 2.1 and/or (2) delayed SUVmax greater than early SUVmax, sensitivity, specificity, and over all accuracy of dual-phase FDG PET/CT were better than that of single phase for less than 25 mm tumor (93%, 83%, and 91% vs 79%, 83%, and 80%, respectively). CONCLUSIONS: Dual-phase FDG PET/CT might be useful for diagnosing small pancreatic tumors.

Factors related to shift from hepatic borderline lesion to overt HCC diagnosed by CT.

BACKGROUND/AIMS: Factors contributing to the shift from the hepatic borderline lesion to overt hepatocellular carcinoma (HCC) were investigated. METHODOLOGY: Ninety-five borderline nodules from 69 patients were followed-up for 6-55 (median 24) months. The borderline lesion was diagnosed when the CT image demonstrated low density in the portal phase and lacked enhancement in the arterial phase. RESULTS: The shift to overt HCC was seen in 32 nodules from 27 patients. Using multivariate analysis, only size was a significant factor contributing to the shift to overt HCC (p = 0.009). The cumulative incidence of the shift to overt HCC was higher in nodules of ≥13 mm in size than in those of < 13 mm (p = 0.034). Among nodules of ≥13 mm, nodules showing iso density in the arterial phase and low density in the portal phase had a higher cumulative incidence of the shift to overt HCC than those showing low density in the arterial and portal phases on CT (p=0.007). CONCLUSIONS: In hepatic borderline nodules diagnosed by CT, greater size, and iso density in the arterial phase and low density in the portal phase may be risk factors associated with the shift to overt HCC.

Predictors of malignancy in branch duct intraductal papillary mucinous neoplasm of the pancreas.

OBJECTIVE: Indication of surgery for branch duct intraductal papillary mucinous neoplasm (BD-IPMN) proposed by the consensus guidelines revised in 2012 was too complex to refer to in clinical practice. This study aimed to identify simple predictors of malignancy in BD-IPMN. METHODS: Consecutive 202 patients with BD-IPMNs were enrolled. They comprised 35 patients that underwent surgery and 167 that were followed up without surgery by being regarded as benign neoplasms. Cutoff values of cyst size, main pancreatic duct (MPD) diameter, and mural nodule size were determined by receiver operator characteristic (ROC) curve. Factors that may discriminate benign from malignant BD-IPMNs were analyzed by multivariate logistic regression model. RESULTS: Cutoff values of cyst size, MPD diameter, and mural nodule size were determined to be 30 mm, 6 mm, and 10 mm, respectively. Multivariate analysis demonstrated that mural nodule ≥10 mm (OR 198, 95% CI 23.1-1690, P<0.0001) and positive cytology (OR 634, 95% CI 49.1-8,190, P<0.0001) were predictors of malignancy in BD-IPMN. When BD-IPMNs with mural nodules ≥10 mm or positive cytology were diagnosed as malignant, sensitivity, specificity, and overall accuracy were 88%, 98%, and 97%, respectively. CONCLUSIONS: Mural nodule ≥10 mm and positive cytology were demonstrated to be simple predictors of malignancy in BD-IPMN.

Alteration of strain ratio evaluated by transabdominal ultrasound elastography may predict the efficacy of preoperative chemoradiation performed for pancreatic ductal carcinoma: preliminary results.

BACKGROUND/AIM: We evaluated the usefulness of ultrasound-elastography (US-elastography) for prediction of therapy effect by measuring strain ratio (SR). METHODOLOGY: Consecutive patients with resectable pancreatic ductal carcinoma who underwent US-elastography before and after neoadjuvant chemoradiation were included. Patients were classified into either response group or non-response group according to the histological evaluation of resected specimens. Serum carbohydrate antigen 19-9 (CA19-9), SR, and maximum standard uptake value (SUVmax) obtained from 18F-fuluoro-deoxy-D-glucose positron emission tomography and computerized tomography were measured before and after chemoradiation. Alteration rate of each parameter was compared between response group and non-response group. RESULTS: Seven patients met the inclusion criteria. One patient was excluded from pancreatectomy because liver metastasis was found by laparotomy. Serum CA19-9 was not elevated for 2 patients throughout the chemoradiation. Three patients were classified into response group and the remaining three into non-response group. Alteration rate of CA19-9 and SR was shown to be grater in response group (26.83 +/- 19.69 vs. 4.87 +/- 4.25, and 3.61 +/- 2.40 vs. 1.39 +/- 0.20, respectively), whereas that of SUVmax was not (1.56 +/- 0.43 vs. 2.11 +/- 0.10). CONCLUSIONS: Increase rate of SR may predict the therapy effect of neoadjuvant chemoradiation for patients with pancreatic ductal carcinoma, especially for patients without elevation of tumor markers.

Potential use of point shear wave elastography for the pancreas: a single center prospective study.

AIM: Clinical use of point shear wave elastography for the liver has been established, however, few studies demonstrated its usefulness for the pancreas. A prospective study was conducted to clarify its feasibility for the pancreas and its usefulness for the identification of high risk group for pancreatic cancer. PATIENTS AND METHODS: Consecutive eighty-five patients underwent point shear wave elastography for the pancreas. The success rate of shear wave velocity (SWV) measurement, that is the number of successful measurements over total 10 measurements, was recorded. The SWV of the pancreas measured at non-tumorous area was compared between patients with and without pancreatic cancer. Factors associated with high SWV were determined by logistic regression model. RESULTS: Sixty patients were included, of these 18 had pancreatic cancer. The success rate of 100% was achieved at the head, the body and the tail of the pancreas in 80%, 83%, and 68% of the patients, respectively. The success rate of ≥80% was achieved in 100%, 100%, and 96% of the patients, respectively. Although mean SWV of the pancreas harboring pancreatic cancer tended to be higher compared with that of the pancreas without cancer (1.51 ± 0.45 m/s vs 1.43 ± 0.28 m/s), they did not reach statistical significance. Multivariate analysis showed that increased amount of alcohol intake was associated with high SWV. CONCLUSION: The SWV of the pancreas was measured with excellent success rate. However, tendency of higher SWV obtained from the pancreas harboring pancreatic cancer needed to be further investigated.

The *1244 A>G polymorphism of MyD88 (rs7744) is closely associated with susceptibility to ulcerative colitis.

Toll­like receptor activation intitially recruits the myeloid differentiation primary response gene (88) (MyD88) protein. A polymorphism *1244 A>G (rs7744) in the 3'­untranslated region of MyD88 has been identified. In the present study, the association of this polymorphism with ulcerative colitis (UC) was investigated. The population studied comprised 922 individuals, including patients with UC (UC cases) and without (controls). Genotyping of rs7744 was performed by PCR single-strand conformation polymorphism and the rs7744 G allele frequencies in the controls and UC cases were 32.8 and 43.5%, respectively (P<0.0001). The results showed that the genotype frequency of the AA homozygote was significantly lower and that of the GG homozygote was significantly higher in the UC cases compared with those in the controls (P=0.0012 for both groups). The rs7744 minor allele variants were significantly associated with susceptibility to UC as indicated by dominant and recessive genetic models. The minor allele variants were associated with an increased risk for UC in the male individuals but not the female individuals. The rs7744 was also associated with a non­continuous phenotype of UC and steroid unused/independent UC. This minor allele homozygote was associated with the disease severity of UC, hospitalization and response to steroid treatment. The results of the present study provided evidence that MyD88 polymorphism rs7744 was significantly associated with the development of UC and that this polymorphism may be associated with the response to treatment therapies for UC.

Functional promoter polymorphisms of NFKB1 influence susceptibility to the diffuse type of gastric cancer.

In the present study, we report an association between gastric cancer and polymorphisms in NFKB1 (rs28362941 and rs78696119). We employed the PCR-SSCP method to detect gene polymorphisms in 479 gastric cancer cases and 880 controls. The rs28362941 del/del homozygote was significantly associated with gastric cancer development; in particular it was closely associated with diffuse type gastric cancer. The rs78696119 GG homozygote was also associated with the diffuse type of gastric cancer. In young subjects, both polymorphisms were significantly associated with the development of gastric cancer. In addition, both polymorphisms were related to tumor progression such as tumor invasion and lymph node metastasis. The inflammatory cell infiltration into non-cancerous gastric mucosa was greater in the subjects with the rs28362491 del/del or rs78696119 GG genotype when compared to those with the other genotypes. In conclusion, functional polymorphisms of NFKB1 are associated with an increased risk of gastric cancer; in particular they are closely associated with the development of diffuse type of gastric cancer via severe gastric inflammation. These polymorphisms also appear to be associated with gastric cancer progression.

Microinvasion of high-grade pancreatic intraepithelial neoplasia.

High-grade pancreatic intraepithelial neoplasia (PanIN-3) is recognized as a precursor lesion of invasive ductal carcinoma (IDC). However, histological evidence that PanIN-3 invades beyond the basement membrane of pancreatic ductal epithelium, that is, the moment PanIN-3 becomes IDC, has not been captured yet. This may be because PanINs which are microscopic papillary or flat lesion rarely develop clinical symptoms and are not detectable on imaging examination. On the other hand, most IDCs were found in the advanced stage with massive invasion. In this report, PanIN-3 obstructed several branch pancreatic ducts and subsequently caused pancreatitis which developed clinical symptom and was detectable as a pancreatic mass in imaging studies. A 65-year-old woman was referred to our institution for further examination of her repeated pancreatitis. Abdominal ultrasound revealed a low echoic mass of 13 mm in diameter in the pancreatic body without upstream dilatation of the main pancreatic duct (MPD). Endoscopic retrograde pancreatography showed a strictured segment of 2 mm in length in the MPD at the pancreatic body. Cytological examination of pancreatic juice revealed adenocarcinoma and distal pancreatectomy was performed. A resected specimen revealed a whitish mass of 15 mm in diameter in the pancreatic body, which was identified as pancreatitis by histological examination. Papillary growth of PanIN-3 was seen mainly in the branch ducts. Each PanIN-3 was located separately in the branch ducts with normal epithelia in the MPD between them. In three adjacent branch ducts, PanIN-3 was observed to be invading microscopically beyond the basement membrane.

Safety and curative ability of endoscopic submucosal dissection for superficial esophageal cancers at least 50 mm in diameter.

BACKGROUND AND AIM: Limited data are available regarding the use of endoscopic submucosal dissection (ESD) for superficial esophageal cancers ≥ 50 mm in diameter. The aim of the present study was to investigate the safety and success of ESD for superficial esophageal cancers ≥ 50 mm. METHODS: A total of 39 patients with superficial esophageal squamous cell carcinoma ≥ 50 mm were treated with ESD at Osaka Medical Center for Cancer and Cardiovascular Diseases between January 2004 and April 2011, and were analyzed in a retrospective study. RESULTS: En bloc resection was achieved in all patients. One mediastinal emphysema without perforation occurred during the procedure. Stricture developed in 11 of 39 patients, requiring a median of five endoscopic balloon dilatation procedures. Thirty-three clinical epithelial or lamina propria mucosal cancers were treated by ESD with curative intent, of which invasion into the muscularis mucosa or deeper was detected in seven and lymphovascular involvement in three. The en bloc resection rate was 100% with a tumor-free margin achieved in 92% of lesions. The curative resection and complication rates during ESD were 70% and 2.5%, respectively. CONCLUSION: ESD achieved a high en bloc resection rate of 92% with a tumor-free margin. Curative resection rate of ESD in patients with clinical epithelial or lamina propria mucosal cancers was not low at 70%. However, the risk of stricture must be taken into account when considering the use of ESD in lesions ≥ 50 mm.

Risk factors of chest pain after endoscopic resection of early esophageal cancer.

BACKGROUND/AIMS: Although endoscopic resection is sometimes associated with chest pain, the risk factors for this complication have not been investigated. METHODOLOGY: From January 2003 to December 2007, 241 patients were treated by endoscopic resection and 139 patients who met our criteria were analyzed. The case group was 40 patients who took an analgesic after endoscopic resection because of chest pain. The controls were 79 patients who did not experience chest pain after endoscopic resection. Twenty patients experienced chest pain, but did not take any analgesics. RESULTS: Although, 60 patients (43%) experienced chest pain, this was treatable by a common analgesic. Univariate analysis revealed that female gender had significant association and resection of posterior wall mucosa had marginal association with chest pain and analgesic use. No significant association with chest pain and analgesic use was found for age, resection method, use of acid suppressing drugs, lesion size and site. Logistic-regression analysis showed that significant risk factors for chest pain and analgesic use were female gender (odds ratio 3.45) and resection of posterior wall mucosa (odds ratio 3.13). CONCLUSIONS: Female gender and resection of posterior wall mucosa were associated with chest pain and analgesic use after endoscopic resection.

Diagnostic clues and subsequent examinations that detected small pancreatic cancer.

BACKGROUND/AIMS: Our aim was to investigate how 2cm or smaller pancreatic cancers were detected successfully in recent years. METHODOLOGY: Diagnostic clues and subsequent examinations that detected 15 histologically confirmed 2 cm or smaller pancreatic cancers were reviewed. RESULTS: Diagnostic clues were imaging findings in 6 patients, symptoms in 5 and laboratory data in 4. Six of 8 patients who had risk factors of pancreatic cancer such as pancreatic cyst, dilated main pancreatic duct, pancreatitis, or diabetes had been followed-up by imaging and laboratory examinations. Five patients with extrapancreatic disease had been followed-up chiefly by laboratory examinations. The remaining 2 had neither of them. Detectabilities of pancreatic mass in US, CT and EUS were 89%, 67% and 100%, respectively; those of pancreatic mass and/or dilated main pancreatic duct were 100% in all three modalities. Cytological examination revealed adenocarcinoma preoperatively in 14 patients (93%). CONCLUSIONS: Small pancreatic cancer of 2 cm or smaller were suggested by symptoms, laboratory data, or imaging examinations. They were confirmed by further examinations including cytology.

Factors predicting perforation during endoscopic submucosal dissection for gastric cancer.

BACKGROUND: Perforation is a common complication of endoscopic submucosal dissection (ESD), but little is known about the relevant risk factors. OBJECTIVE: To investigate the risk factors for perforation. DESIGN: Retrospective study. SETTING: A cancer referral center. PATIENTS: A total of 1795 early gastric tumors in 1500 patients treated by ESD from July 2002 to December 2010 were included in the analysis. MAIN OUTCOME MEASUREMENTS: The associations between the incidence of perforation and patient and lesion characteristics were investigated. RESULTS: Perforation during ESD occurred in 50 lesions (2.8%). Univariate analysis identified tumor location (upper, middle, or lower stomach), tumor diameter (≤ 20 or >20 mm), and treatment period (lesions treated in the first or second period) as predictors of perforation. Multivariate analysis identified tumor location (upper stomach), tumor diameter (>20 mm), and treatment period (first half) as independent risk factors for perforation. The odds ratios were 2.4 (95% CI, 1.3-4.7; P = .006) for lesions in the upper stomach and 1.9 (95% CI, 1.0-3.5; P = .04) for lesions larger than 20 mm. Perforation risks were 5.4% for lesions in the upper stomach and 4.4% for lesions larger than 20 mm. Three patients required emergency surgery, but the rest of the patients were successfully treated with endoscopic clipping. There was no perforation-related mortality. LIMITATIONS: Single-center, retrospective study design. CONCLUSIONS: Lesions in the upper stomach and lesions larger than 20 mm were independent risk factors for perforation during ESD. Patients should be made aware of the estimated high risks of these lesions before undergoing ESD.