1.Diagnosis of pancreatic ductal carcinoma
Susumu Hijioka ; Kazuo Hara ; Nobumasa Mizuno ; Hiroshi Imaoka ; Kenji Yamao
Innovation 2014;8(4):100-101
Pancreatic ductal adenocarcinoma (PDAC) is the most lethal type of gastrointestinal
cancer, with a 5-year survival rate of 5%; it remains a significant, unresolved
therapeutic challenge. Its aggressive features include insidious presentation,
unresectability due to early involvement of major vessels, debilitating symptoms
at the late stage and de novo chemoresistance.
However, according to the Japan Pancreatic Cancer Registry, the 5-year survival
of UICC Stages 0 and 1a are 85.8% and 68.7%, respectively.
Early diagnosis plays an important role in improving the overall survival of
patients with PDAC; therefore, efforts should focus on early diagnosis and the
reliable identification of patients who will most likely benefit from major surgical
intervention.
Patients with risk factors, including family history, accompanying disease,
diabetes mellitus, chronic pancreatitis and intraductal papillary mucinous
neoplasms (IPMN), should be followed up for early detection of PDAC. In Japan,
a national team has undertaken such surveillance of patients with IPMN. The
protocol comprises a semi-annual follow up using various modalities to detect
not only IPMN carcinoma, but also PDAC concomitant with IPMN. I will address
this protocol in detail.
The most accurate imaging technique for PDAC diagnosis and staging is
considered to be contrast-enhanced computed tomography (CECT). Whereas
CT should be the first choice in patients with suspected PDAC, endoscopic
ultrasound (EUS) is the most accurate, particularly for detecting small lesions (<
10 mm). EUS combines the potential of endoscopy, which enables visualization
of the mucosal surface of the gastrointestinal (GI) tract, with ultrasonography.
Thus, EUS is able to provide detailed, high-resolution images of the pancreas.
However, whether a lesion is malignant or benign is unable to be discriminated
solely from EUS imaging features. Obtaining samples from suspicious lesions or
lymph nodes using EUS-guided fine-needle aspiration (FNA), offers the potential
for cytological or histological diagnoses of pancreatic lesions with high sensitivity
and specificity. Since accurate preoperative evaluation is essential to select the
appropriate management strategy, the roles of EUS and EUS-FNA are crucial.
Stage 0 PDAC (carcinoma in situ) has recently been discovered. This stage of PDAC
is unable to be diagnosed using EUS-FNA, because EUS-FNA is only applicable
after PDAC forms a cancerous mass (worse than stage1). Thus, diagnostic methods
other than imaging require development. Presently, endoscopic retrograde
pancreatography (ERP) combined with cytology is able to detect Stage 0 PDAC,
and in Japan, nasopancreatic drainage tubes have recently been used to collect
pancreatic juice for cytodiagnosis. I would also like to introduce this method.
2. Diagnosis of pancreatic ductal carcinoma
Susumu HIJIOKA ; Kazuo HARA ; Nobumasa MIZUNO ; Hiroshi IMAOKA ; Kenji YAMAO
Innovation 2014;8(4):100-101
Pancreatic ductal adenocarcinoma (PDAC) is the most lethal type of gastrointestinalcancer, with a 5-year survival rate of 5%; it remains a significant, unresolvedtherapeutic challenge. Its aggressive features include insidious presentation,unresectability due to early involvement of major vessels, debilitating symptomsat the late stage and de novo chemoresistance.However, according to the Japan Pancreatic Cancer Registry, the 5-year survivalof UICC Stages 0 and 1a are 85.8% and 68.7%, respectively.Early diagnosis plays an important role in improving the overall survival ofpatients with PDAC; therefore, efforts should focus on early diagnosis and thereliable identification of patients who will most likely benefit from major surgicalintervention.Patients with risk factors, including family history, accompanying disease,diabetes mellitus, chronic pancreatitis and intraductal papillary mucinousneoplasms (IPMN), should be followed up for early detection of PDAC. In Japan,a national team has undertaken such surveillance of patients with IPMN. Theprotocol comprises a semi-annual follow up using various modalities to detectnot only IPMN carcinoma, but also PDAC concomitant with IPMN. I will addressthis protocol in detail.The most accurate imaging technique for PDAC diagnosis and staging isconsidered to be contrast-enhanced computed tomography (CECT). WhereasCT should be the first choice in patients with suspected PDAC, endoscopicultrasound (EUS) is the most accurate, particularly for detecting small lesions (<10 mm). EUS combines the potential of endoscopy, which enables visualizationof the mucosal surface of the gastrointestinal (GI) tract, with ultrasonography.Thus, EUS is able to provide detailed, high-resolution images of the pancreas.However, whether a lesion is malignant or benign is unable to be discriminatedsolely from EUS imaging features. Obtaining samples from suspicious lesions orlymph nodes using EUS-guided fine-needle aspiration (FNA), offers the potentialfor cytological or histological diagnoses of pancreatic lesions with high sensitivityand specificity. Since accurate preoperative evaluation is essential to select theappropriate management strategy, the roles of EUS and EUS-FNA are crucial.Stage 0 PDAC (carcinoma in situ) has recently been discovered. This stage of PDACis unable to be diagnosed using EUS-FNA, because EUS-FNA is only applicableafter PDAC forms a cancerous mass (worse than stage1). Thus, diagnostic methodsother than imaging require development. Presently, endoscopic retrogradepancreatography (ERP) combined with cytology is able to detect Stage 0 PDAC,and in Japan, nasopancreatic drainage tubes have recently been used to collectpancreatic juice for cytodiagnosis. I would also like to introduce this method.
3.Utility of Forward-View Echoendoscopy for Transcolonic Fine-Needle Aspiration of Extracolonic Lesions: An Institutional Experience
Nithi THINRUNGROJ ; Kazuo HARA ; Nobumasa MIZUNO ; Takamichi KUWAHARA ; Nozomi OKUNO
Clinical Endoscopy 2020;53(1):60-64
Background/Aims:
Non-invasive tissue sampling from the lower intra-abdominal and pelvic cavity is challenging. The role of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in this situation is not well-established because of the limitations of the curved linear-array echoendoscopy-EUS for colonic insertion. The aim of this study was to report our institutional experience of transcolonic EUS-FNA using forward-viewing therapeutic linear echoendoscopy-EUS (FV-EUS) in combination with fluoroscopic guidance.
Methods:
Medical records of 13 patients who underwent transcolonic EUS-FNA of extracolonic lesions using FV-EUS in combination with fluoroscopic guidance at Aichi Cancer Center Hospital, Nagoya, Japan from June 2015 to November 2018 were retrospectively reviewed.
Results:
Using FV-EUS under fluoroscopic guidance, the FNA procedure could be performed successfully in all patients (100% technical success), with a median procedure time of 31 minutes. The sensitivity, specificity, and accuracy of EUS-FNA for detecting malignant lesions in this study were 91%, 100%, and 92%, respectively. There were no adverse events associated with the EUS-FNA procedure.
Conclusions
FV-EUS in combination with fluoroscopic guidance is an easy, safe, and effective technique for FNA of extracolonic lesions in the lower abdomen.
4.Does the WHO 2010 classification of pancreatic neuroendocrine neoplasms accurately characterize pancreatic neuroendocrine carcinomas?
Tsukasa Yoshida ; Susumu Hijioko ; Waki Hosoda ; Nobumasa Mizuno ; Kazuo Hara ; Hiroshi Imaoka ; Vikram Bhatia ; Masahiro Tajika ; Mohamed A Mekky ; Makoto Ishihara ; Tatsuji Yogi ; Kenji Yamao
Innovation 2014;8(4):124-125
Background: The WHO classified pancreatic neuroendocrine neoplasms (pNEN)
in 2010 as G1, G2, and neuroendocrine carcinoma (NEC), according to Ki67
labeling index (LI). However, the clinical behavior of NEC is still not fully studied.
We aimed to clarify the clinicopathological and molecular characteristics of
NECs.
Methods: We retrospectively evaluated the clinicopathological characteristics,
KRAS mutation status, treatment response, and the overall survival of eleven
pNEC patients diagnosed between 2001 and 2014 according to the WHO 2010.
We subclassified WHO-NECs into well-differentiated (WDNEC) and poorlydifferentiated
NEC (PDNEC), the latter further subdivided into large and small
cell type.
Results: The median Ki67 LI was 69.1% (range, 40% - 95%) and the median
tumor size was 35 mm. 11 WHO-NECs were subclassified 4 WDNEC and 7
PDNEC, and further separated PDNEC into 3 large cell and 4 small cell subtypes.
Comparisons of WDNEC vs. PDNEC revealed hypervascularity on CT, 50% (2/4)
vs. 0% (0/7) (P = 0.109); median Ki67 LI, 46.3% (40% - 53%) vs. 85% (54% -
95%) (P = 0.001); KRAS mutations, 0% (0/4) vs. 85.7% (6/7) (P = 0.015); response
rates to platinum-based chemotherapy, 0% (0/2) vs.100% (4/4) (P = 0.067) and
median survival, 227 vs. 186 days (P = 0.227).
Conclusions: The WHO-NEC category may be composed of heterogeneous
disease entities, namely WDNEC and PDNEC. These subgroups tended to exhibit
differing Ki67 and KRAS mutation profiles, and distinct response to chemotherapy.
Further studies for the re-evaluation of the current WHO 2010 classification is
warranted.
5.High-Resolution Probe-Based Confocal Laser Endomicroscopy for Diagnosing Biliary Diseases
Hiroki KODA ; Kazuo HARA ; Okuno NOZOMI ; Takamichi KUWAHARA ; Mizuno NOBUMASA ; Shin HABA ; Miyano AKIRA ; Isomoto HAJIME
Clinical Endoscopy 2021;54(6):924-929
Probe-based confocal laser endomicroscopy is an endoscopic technique that enables in vivo histological evaluation using fluorescent pigment. The ability to diagnostically differentiate between benign and malignant biliary disease using the “CholangioFlexTM”, a dedicated biliary device, has been reported. However, the Miami and Paris classifications, used as diagnostic criteria, mainly evaluate findings in the submucosa, and visualizing the epithelium as the main site of lesions remains difficult. To address this problem, we verified the imaging findings and diagnostic ability of three types of probes: CholangioFlexTM, GastroFlexTM, and AlveoFlexTM. With GastroFlexTM, the clear mucosal epithelium was observed, and differential diagnoses as benign/malignant could be made based on epithelial findings. GastroFlexTM may be a good first-choice probe for probe-based confocal laser endomicroscopy of biliary diseases, and a new diagnostic classification based on bile duct epithelial findings may provide useful criteria independent of the Miami or Paris classifications.
6.Clinical utility of endoscopic ultrasound-guided tissue acquisition for comprehensive genomic profiling of pancreatic cancer
Nozomi OKUNO ; Kazuo HARA ; Nobumasa MIZUNO ; Shin HABA ; Takamichi KUWAHARA ; Yasuhiro KURAISHI ; Daiki FUMIHARA ; Takafumi YANAIDANI
Clinical Endoscopy 2023;56(2):221-228
Background/Aims:
Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is essential for the diagnosis of pancreatic cancer. The feasibility of comprehensive genomic profiling (CGP) using samples obtained by EUS-TA has been under recent discussion. This study aimed to evaluate the utility of EUS-TA for CGP in a clinical setting.
Methods:
CGP was attempted in 178 samples obtained from 151 consecutive patients with pancreatic cancer at the Aichi Cancer Center between October 2019 and September 2021. We evaluated the adequacy of the samples for CGP and determined the factors associated with the adequacy of the samples obtained by EUS-TA retrospectively.
Results:
The overall adequacy for CGP was 65.2% (116/178), which was significantly different among the four sampling methods (EUS-TA vs. surgical specimen vs. percutaneous biopsy vs. duodenal biopsy, 56.0% [61/109] vs. 80.4% [41/51] vs. 76.5% [13/17] vs. 100.0% [1/1], respectively; p=0.022). In a univariate analysis, needle gauge/type was associated with adequacy (22 G fine-needle aspiration vs. 22 G fine-needle biopsy [FNB] vs. 19 G-FNB, 33.3% (5/15) vs. 53.5% (23/43) vs. 72.5% (29/40); p=0.022). The sample adequacy of 19 G-FNB for CGP was 72.5% (29/40), and there was no significant difference between 19 G-FNB and surgical specimens (p=0.375).
Conclusions
To obtain adequate samples for CGP with EUS-TA, 19 G-FNB was shown to be the best in clinical practice. However, 19 G-FNB was not still sufficient, so further efforts are required to improve adequacy for CGP.
7. Does the WHO 2010 classification of pancreatic neuroendocrine neoplasms accurately characterize pancreatic neuroendocrine carcinomas?
Tsukasa YOSHIDA ; Susumu HIJIOKO ; Waki HOSODA ; Nobumasa MIZUNO ; Kazuo HARA ; Hiroshi IMAOKA ; Vikram BHATIA ; Masahiro TAJIKA ; Mohamed A Mekky ; Makoto ISHIHARA ; Tatsuji YOGI ; Kenji YAMAO
Innovation 2014;8(4):124-125
Background: The WHO classified pancreatic neuroendocrine neoplasms (pNEN)in 2010 as G1, G2, and neuroendocrine carcinoma (NEC), according to Ki67labeling index (LI). However, the clinical behavior of NEC is still not fully studied.We aimed to clarify the clinicopathological and molecular characteristics ofNECs.Methods: We retrospectively evaluated the clinicopathological characteristics,KRAS mutation status, treatment response, and the overall survival of elevenpNEC patients diagnosed between 2001 and 2014 according to the WHO 2010.We subclassified WHO-NECs into well-differentiated (WDNEC) and poorlydifferentiatedNEC (PDNEC), the latter further subdivided into large and smallcell type.Results: The median Ki67 LI was 69.1% (range, 40% - 95%) and the mediantumor size was 35 mm. 11 WHO-NECs were subclassified 4 WDNEC and 7PDNEC, and further separated PDNEC into 3 large cell and 4 small cell subtypes.Comparisons of WDNEC vs. PDNEC revealed hypervascularity on CT, 50% (2/4)vs. 0% (0/7) (P = 0.109); median Ki67 LI, 46.3% (40% - 53%) vs. 85% (54% -95%) (P = 0.001); KRAS mutations, 0% (0/4) vs. 85.7% (6/7) (P = 0.015); responserates to platinum-based chemotherapy, 0% (0/2) vs.100% (4/4) (P = 0.067) andmedian survival, 227 vs. 186 days (P = 0.227).Conclusions: The WHO-NEC category may be composed of heterogeneousdisease entities, namely WDNEC and PDNEC. These subgroups tended to exhibitdiffering Ki67 and KRAS mutation profiles, and distinct response to chemotherapy.Further studies for the re-evaluation of the current WHO 2010 classification iswarranted.
8.Endoscopic ultrasound-guided portal vein coiling: troubleshooting interventional endoscopic ultrasonography
Shin HABA ; Kazuo HARA ; Nobumasa MIZUNO ; Takamichi KUWAHARA ; Nozomi OKUNO ; Akira MIYANO ; Daiki FUMIHARA ; Moaz ELSHAIR
Clinical Endoscopy 2022;55(3):458-462
Endoscopic ultrasound (EUS)-guided hepaticogastrostomy (HGS) is widely performed not only as an alternative to transpapillary biliary drainage, but also as primary drainage for malignant biliary obstruction. For anatomical reasons, this technique carries an unavoidable risk of mispuncturing intrahepatic vessels. We report a technique for troubleshooting EUS-guided portal vein coiling to prevent bleeding from the intrahepatic portal vein after mispuncture during interventional EUS. EUS-HGS was planned for a 59-year-old male patient with unresectable pancreatic cancer. The dilated bile duct (lumen diameter, 2.8 mm) was punctured with a 19-gauge needle, and a guidewire was inserted. After bougie dilation, the guidewire was found to be inside the intrahepatic portal vein. Embolizing coils were placed to prevent bleeding. Embolization coils were successfully inserted under stabilization of the catheter using a double-lumen cannula with a guidewire. Following these procedures, the patient was asymptomatic. Computed tomography performed the next day revealed no complications.
9.Safety and feasibility of opening window fistulotomy as a new precutting technique for primary biliary access in endoscopic retrograde cholangiopancreatography
Yasuhiro KURAISHI ; Kazuo HARA ; Shin HABA ; Takamichi KUWAHARA ; Nozomi OKUNO ; Takafumi YANAIDANI ; Sho ISHIKAWA ; Tsukasa YASUDA ; Masanori YAMADA ; Nobumasa MIZUNO
Clinical Endoscopy 2023;56(4):490-498
Background/Aims:
Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most common and serious complication of endoscopic retrograde cholangiopancreatography. To prevent this event, a unique precutting method, termed opening window fistulotomy, was performed in patients with a large infundibulum as the primary procedure for biliary cannulation, whereby a suprapapillary laid-down H-shaped incision was made without touching the orifice. This study aimed to assess the safety and feasibility of this novel technique.
Methods:
One hundred and ten patients were prospectively enrolled in this study. Patients with a papillary roof size ≥10 mm underwent opening window fistulotomy for primary biliary access. In addition, the incidence of complications and success rate of biliary cannulation were evaluated.
Results:
The median size of the papillary roof was 6 mm (range, 3–20 mm). Opening window fistulotomy was performed in 30 patients (27.3%), none of whom displayed PEP. Duodenal perforation was recorded in one patient (3.3%), which was resolved by conservative treatment. The cannulation rate was high (96.7%, 29/30 patients). The median duration of biliary access was 8 minutes (range, 3–15 minutes).
Conclusions
Opening window fistulotomy demonstrated its feasibility for primary biliary access by achieving great safety with no PEP complications and a high success rate for biliary cannulation.
10.Refractory benign biliary stricture due to chronic pancreatitis in two patients treated using endoscopic ultrasound-guided choledochoduodenostomy fistula creation: case reports
Sho ISHIKAWA ; Nozomi OKUNO ; Kazuo HARA ; Nobumasa MIZUNO ; Shin HABA ; Takamichi KUWAHARA ; Yasuhiro KURAISHI ; Takafumi YANAIDANI
Clinical Endoscopy 2024;57(1):122-127
Benign biliary stricture (BBS) is a complication of chronic pancreatitis (CP). Despite endoscopic biliary stenting, some patients do not respond to treatment, and they experience recurrent cholangitis. We report two cases of CP with refractory BBS treated using endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) fistula creation. A 50-year-old woman and a 60-year-old man both presented with obstructive jaundice secondary to BBS due to alcoholic CP. They underwent repeated placement of a fully covered self-expandable metal stent for biliary strictures. However, the strictures persisted, causing repeated episodes of cholangitis. Therefore, an EUS-CDS was performed. The stents were eventually removed and the patients became stent-free. These fistulas have remained patent without cholangitis for more than 2.5 years. Fistula creation using EUS-CDS is an effective treatment option for BBS.