Phase II Study of Continued Trastuzumab Plus Irinotecan in Patients with HER2-positive Gastric Cancer Previously Treated with Trastuzumab (HGCSG 1201).

BACKGROUND: The efficacy of irinotecan plus continuous trastuzumab beyond progression in patients with gastric cancer previously treated with trastuzumab plus standard first-line chemotherapy has not been reported. METHODS: Patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer who were previously treated with trastuzumab received trastuzumab every 3 weeks and irinotecan every 2 weeks. The primary endpoint was the overall response rate (ORR), and the secondary endpoints included progression-free survival (PFS), 6-month survival rates, safety, and subgroup analysis by HER2 status. RESULTS: Sixteen patients were enrolled in a 3-year pre-planned registration period. This study was prematurely closed due to poor patient accrual. The ORR and disease control rate were 6.7% (95% CI, 0.2-32.0) and 53.3% (95% CI, 26.6-78.7). The median PFS and overall survival (OS) were 2.4 months (95% CI, 0.0-5.2) and 9.7 months (95% CI, 8.2-11.2), respectively. The most frequently reported grades 3-4 adverse events were neutropenia (40%), anemia (27%), anorexia (33%), and fatigue (33%). CONCLUSION: With only 16 patients enrolled, the present study has very low power to detect any clinical benefit of trastuzumab plus irinotecan beyond disease progression in patients with HER2-positive advanced gastric cancer who previously received trastuzumab.Trial Identifier: UMIN000007636.

Risk of Pancreatitis Following Biliary Stenting With/Without Endoscopic Sphincterotomy: A Randomized Controlled Trial.

BACKGROUND & AIMS: The efficacy of endoscopic sphincterotomy (ES) before endoscopic transpapillary biliary drainage in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) has not been established. The aim of this study was to evaluate the effect of performing ES before biliary stent/tube placement on the occurrence of PEP. METHODS: Three hundred seventy patients with biliary stricture requiring endoscopic biliary stenting were enrolled and randomly allocated to the ES group (n = 185) or non-ES group (n = 185). All participants were followed up for 30 days after the procedure. The data and occurrence of adverse events were prospectively collected. The primary outcome measure of this study was the incidence of PEP within 2 days of initial transpapillary biliary drainage. Secondary outcome measures were the incidence of other adverse events related to biliary stent/tube placement. RESULTS: PEP occurred in 36 patients (20.6%) in the non-ES group and in 7 patients (3.9%) in the ES group (P < .001). The difference in the incidence of PEP between the 2 groups in the per-protocol population was 16.7% (95% confidence interval, 10.1%-23.3%), which was not within the noninferiority margin of 6%. Except for bleeding, the incidences of other adverse events were not significantly different between the groups. CONCLUSION: ES before endoscopic biliary stenting could have the preventive effect on the occurrence of PEP in patients with biliary stricture. University Hospital Medical Information Network Number, UMIN000025727.University Hospital Medical Information Network Clinical Trial Registry URL: https://www.umin.ac.jp/ctr/index.htm.

Severe spruelike enteropathy and collagenous colitis caused by olmesartan.

BACKGROUND: Olmesartan, which is an angiotensin II receptor blocker, reportedly causes spruelike enteropathy, with intestinal villous atrophy as its typical histopathological finding. Interestingly, collagenous and/or lymphocytic gastritis and colitis occur in some patients. We report the case of a 73-year-old Japanese man with a 2-month clinical history of severe diarrhea and weight loss. There were few reports in which spruelike enteropathy and collagenous colitis were both observed and could be followed up. CASE PRESENTATION: We report a case of a 73-year-old man with a 2-month clinical history of severe diarrhea and weight loss. He had taken olmesartan for hypertension treatment for 5 years. Endoscopic examination with biopsies revealed intestinal villous atrophy and collagenous colitis. Suspecting enteropathy caused by olmesartan, which was discontinued on admission because of hypotension, we continued to stop the drug. Within 3 weeks after olmesartan discontinuation, his clinical symptoms improved. After 3 months, follow-up endoscopy showed improvement of villous atrophy but not of the thickened collagen band of the colon. However, the mucosa normalized after 6 months, histologically confirming that the preexistent pathology was finally resolved. CONCLUSIONS: This report presents a case in which spruelike enteropathy and collagenous colitis were both observed and could be followed up. In unexplained cases of diarrhea, medication history should be reconfirmed and this disease should be considered a differential diagnosis.

IFN-λ3 as a host immune response in acute hepatitis E virus infection.

BACKGROUND AND AIM: Hepatitis E virus (HEV) is mainly transmitted orally, either waterborne or zoonotic foodborne. Intestinal viruses such as rotavirus are known to induce type III interferon (IFN) in the gastrointestinal (GI) tract where type III IFN dominantly functions in comparison with type I IFN. Therefore, the aim of this study is to investigate the significance of type III IFN (IFN-λ3) in acute hepatitis E. METHODS: IFN-λ3 and HEV RNA levels in the sera of patients with acute HEV infection and in the supernatant of HEV-inoculated cells were measured, using an in-house high-sensitivity method and reverse transcription-polymerase chain reaction, respectively. RESULTS: High serum IFN-λ3 levels were found in the early phase of acute HEV infection, which normalized after resolution. Interestingly, serum IFN-λ3 levels correlated well with serum HEV RNA titers in the same sera, both of which showed the peak before the robust increase of transaminases. In vitro experiments demonstrated that HEV replicated well in the cells with little IFN-λ3 induction (Caco-2, A549) and recombinant IFN-λ3 inhibited HEV replication in a dose-dependent manner. In contrast, in HT-29 cells, a colon cancer cell line, HEV poorly replicated and induced IFN-λ3 in a titer-dependent manner. CONCLUSIONS: These clinical and experimental observations suggest that HEV induced IFN-λ3 as a host innate immune response, which may play a protective role against HEV.

Analysis of the optimal psoas muscle mass index cut-off values, as measured by computed tomography, for the diagnosis of loss of skeletal muscle mass in Japanese people.

This study aimed to determine the optimal psoas muscle mass index (PMI) cut-off values for diagnosis of skeletal muscle mass loss. METHODS: We evaluated PMI in two groups of normal controls: a medical check-up group and a liver donation candidate group. We analyzed two novel PMI cut-off values, one based on the mean - two standard deviations (2SD) and one based on the lower 5%. Skeletal muscle mass index (SMI) evaluations using computed tomography (sliceOmatic; TomoVision) and bioelectrical impedance analysis and PMI evaluation were undertaken simultaneously. We analyzed the correlation between our PMI cut-off values and the Japan Society of Hepatology-defined SMI cut-off values. The prevalence of skeletal muscle mass loss in patients with liver disease was assessed using the novel PMI cut-off values. RESULTS: In 504 normal controls aged ≤50 years, the PMI cut-off values based on mean -2SD and the lower 5% were set at 3.30 cm2 /m2 for men and 1.69 cm2 /m2 for women and 3.74 cm2 /m2 for men and 2.29 cm2 /m2 for women, respectively. The PMI cut-off values based on the lower 5% alone showed that skeletal muscle mass loss increased with age. Furthermore, they correlated well with Japan Society of Hepatology-defined SMI (sliceOmatic) cut-off values and showed a significantly higher prevalence of skeletal muscle mass loss in patients with liver cirrhosis than those without liver cirrhosis. CONCLUSIONS: We propose the following PMI cut-off values: 3.74 cm2 /m2 for male individuals and 2.29 cm2 /m2 for female individuals. These cut-off values can facilitate accurate diagnosis and management of sarcopenia in patients with chronic liver disease.

Safety and efficacy of sofosbuvir and ribavirin for genotype 2 hepatitis C Japanese patients with renal dysfunction.

AIM: The safety and efficacy of sofosbuvir (SOF) and ribavirin (RBV) have not been well clarified in patients with renal dysfunction because clinical trials have not included such patients. We evaluated the safety and efficacy of SOF and RBV for genotype 2 hepatitis C virus (HCV)-infected patients with renal dysfunction. METHODS: The study included genotype 2 HCV-infected patients who received SOF and RBV between July 2014 and May 2017. The sustained virologic response (SVR) after the treatment and safety during the therapy were evaluated according to renal function. RESULTS: A total of 231 patients were included in this study. The median age was 62 years old, and 45.9% (106/231) were men. Of the 231 patients, 191 (82.8%) and 40 (17.2%) were classified as having chronic kidney disease (CKD) stages G1/2 and G3, respectively. The overall SVR rate was 97% (224/231). The SVR rates in patients with CKD stages G1, 2, G3a, and G3b were 98.1%, 98.6%, 87.9%, and 100%, respectively, and this therapy was tolerated. Multivariate analysis indicated that renal dysfunction was significantly associated with a non-SVR (odds ratio, 6.963; 95% confidence interval, 1.494-32.41; P = 0.013). The patients with renal dysfunction were older, had advanced liver fibrosis, lower baseline platelet and hemoglobin levels, and a higher rate of RBV dose reduction. CONCLUSIONS: Sofosbuvir and RBV therapy is highly effective and safe for genotype 2 HCV-infected Japanese patients. However, attention should be paid to baseline renal function when SOF- and RBV-containing regimens are used for patients with renal dysfunction.

Study protocol of HGCSG1404 SNOW study: a phase I/II trial of combined chemotherapy of S-1, nab-paclitaxel and oxaliplatin administered biweekly to patients with advanced gastric cancer.

BACKGROUND: In Japan, S-1 plus cisplatin (SP) regimen has become a standard therapy for patients with advanced gastric cancer. Moreover, the S-1 plus oxaliplatin regimen is now a standard treatment. Nab-paclitaxel was developed for chemotherapy of gastric cancer in Japanese clinical practice. Nab-paclitaxel, created with albumin-bound paclitaxel particles, has high transferability to tumour tissues and does not cause hypersensitivity reactions because of a different chemical composition compared with docetaxel and paclitaxel. A combination of S-1, nab-paclitaxel and oxaliplatin (which we named 'SNOW regimen') can be a promising triplet therapy for advanced gastric cancer. Although we have to pay attention to chemotherapy-induced neuropathy, we aim to investigate the recommended dose of this regimen in a phase I study. Furthermore, we will investigate its efficacy and toxicity in a phase II study. METHODS: The phase I study is a dose-escalation study using a standard 3 plus 3 design, followed by expansion cohorts. The SNOW regimen involves 28-day cycles with escalated doses of nab-paclitaxel (100-175 mg/m2 on days 1 and 15) and fixed doses of oxaliplatin (65 mg/ m2 on days 1 and 15) and S-1 (80 mg/m2/day on day 1 to 14). The primary endpoints are assessment of dose limiting toxicities and determination of maximum tolerated dose to investigate the recommended dose in the subsequent phase II study. In the phase II study, the primary endpoint is objective response rate. Secondary endpoints are assessment of safety, progression-free survival, disease control rate, overall survival and time to treatment failure. Adverse events were monitored and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. DISCUSSION: Triplet therapies for advanced gastric cancer patients have been evaluated in clinical trials. The SNOW regimen can be a promising new triplet therapy. TRIAL REGISTRATION: This study is performed at institutes that participate in Hokkaido Gastrointestinal Cancer Study Group (HGCSG) and registered as UMIN000016788 . Registrated 16 March 2015.

Early use of double-guidewire technique to facilitate selective bile duct cannulation: the multicenter randomized controlled EDUCATION trial.

BACKGROUND AND STUDY AIMS: There are no guidelines for the timing of conversion from a single-guidewire to a double-guidewire technique to facilitate selective bile duct cannulation and reduce post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP), when using wire-guided cannulation. We investigated whether early conversion to the double-guidewire method, at first unintentional insertion of a guidewire into the pancreatic duct, facilitated selective bile duct cannulation and reduced PEP compared with repeated single-guidewire attempts. PATIENTS AND METHODS: A multicenter prospective randomized controlled trial included 274 patients with a naive papilla, undergoing endoscopic retrograde cholangiography (ERC) using wire-guided cannulation in whom there was unintentional insertion of the guidewire into the pancreatic duct. With the guidewire still in the duct, patients were randomly assigned to undergo the double-guidewire technique or repeated single-wire cannulation. Main outcomes were success rates for selective bile duct cannulation and PEP frequency. RESULTS: Success rates for selective bile duct cannulation within 10 attempts and 10 minutes were 75 % and 70 %, respectively, for the early double-guidewire (EDG) and repeated single-guidewire (RSG) cannulation groups (relative rate 1.07, 95 % confidence interval [95 %CI] 0.93 - 1.24, P = 0.42). Corresponding final selective bile duct cannulation rates were 98 % and 97 % (relative rate 1.01, 95 %CI 0.97 - 1.05, P = 1.00). PEP rates were 20 % and 17 %, respectively, for the EDG and RSG cannulation groups (relative risk 1.17, 95 %CI 0.71 - 1.94, P = 0.53). Double-guidewire cannulation was more effective in patients with malignant biliary stricture (relative rate 1.36, 95 %CI 1.05 - 1.77, P = 0.02). CONCLUSIONS: During therapeutic ERC using wire-guided cannulation, converting to a double-guidewire technique neither facilitated selective bile duct cannulation nor decreased PEP incidence compared with repeated use of a single-wire technique.

Randomized controlled trial on the skin toxicity of panitumumab in Japanese patients with metastatic colorectal cancer: HGCSG1001 study; J-STEPP.

AIM: We planned a randomized, open-label trial to evaluate differences between pre-emptive and reactive skin treatment for panitumumab (Pmab)-associated skin toxicities in Japanese patients with metastatic colorectal cancer. PATIENTS & METHODS: Patients receiving third-line Pmab-containing regimens were randomized to pre-emptive or reactive treatment. The primary end point was the cumulative incidence of ≥grade 2 skin toxicities during 6 weeks. Retrospectively, a dermatologist reviewed skin toxicities, in a blinded manner. RESULTS: A total of 95 patients were enrolled (pre-emptive: 47, reactive: 48). The primary end point was achieved (21.3 and 62.5% [risk ratio: 0.34; p < 0.001], for pre-emptive and reactive treatment, respectively). A similar trend was observed in central review. CONCLUSION: Pre-emptive skin treatment could reduce the severity of Pmab-associated skin toxicities in Japanese metastatic colorectal cancer patients.

Technical difficulty according to location, and risk factors for perforation, in endoscopic submucosal dissection of colorectal tumors.

BACKGROUND: Colorectal endoscopic submucosal dissection (ESD) is a widely accepted treatment for colorectal tumors, but is technically more difficult and has a higher risk of complications such as perforation than gastric ESD. Few studies have investigated the factors associated with technical difficulty and perforation in colorectal ESD. This study aimed to evaluate the technical difficulty according to location, and the risk factors for perforation, in colorectal ESD. METHODS: This retrospective study included 134 consecutive colorectal tumors treated by ESD in 122 patients at the Division of Endoscopy of Hokkaido University Hospital and the Department of Gastroenterology of Kitami Red Cross Hospital from November 2011 to February 2013. To evaluate the technical difficulty of performing ESD for colorectal tumors at specific locations, the en bloc R0 resection rate, specimen diameter, procedure speed, and procedure time were compared among tumor locations using the χ (2) test or analysis of variance. Risk factors for perforation were identified by multiple logistic regression analysis. RESULTS: The en bloc R0 resection rate was 86.6 % (116/134), the mean tumor diameter was 27.1 mm, and the mean procedure time was 63.5 min. The mean speed of procedures was significantly slower in the sigmoid colon (24.7 min/cm(2)) than in other areas. Perforation occurred in nine cases (6.7 %). Submucosal fibrosis was the only factor independently associated with perforation (odds ratio 5.684, 95 % confidence interval 1.307-24.727). CONCLUSIONS: ESD was slower for sigmoid colon tumors than for tumors in other areas, suggesting that ESD was technically more difficult in the sigmoid colon than in other colorectal areas. Submucosal fibrosis was independently associated with perforation during colorectal ESD.

Critical evaluation of the modified Rankin Scale for assessment of the efficacy of mechanical thrombectomy: A retrospective comparison between the modified Rankin Scale and functional independence measure.

OBJECTIVE: The primary outcome measure used in mechanical thrombectomy (MT) trials is the modified Rankin Scale (mRS). However, the accuracy of mRS might be limited. On the other hand, the functional independence measure (FIM) is a widely used tool to quantify the extent to which patients require assistance during their activities of daily living. The current study aimed to reveal different clinical backgrounds that affect the efficacy of MT measured either by mRS or FIM. METHODS: Patients who underwent MT at our institution from January 2019 to July 2022 were included and divided into groups based on mRS scores of 0-2 and ≥ 3. Patients were also divided into two groups based on a cut-off value of FIM of ≥ 108, as patients with FIM ≥ 108 are capable of living an independent life. RESULTS: The mRS score was 0-2 in 33% of the patients, while the FIM score was ≥ 108 in only 15% of the patients. In the mRS groups, there were significant differences in terms of duration of hospitalization, National Institutes of Health Stroke Scale (NIHSS) scores, achievement of thrombolysis in cerebral infarction (TICI) reperfusion grade of 2b or 3, and postoperative bleeding. Multivariate logistic regression analysis revealed that NIHSS score and achievement of TICI 2b or 3 were significant factors related to mRS 0-2 at discharge. The FIM groups differed significantly in terms of age and, duration of hospitalization, NIHSS score, although multivariate logistic regression analysis revealed that only the NIHSS score was significantly associated with an FIM score of ≥ 108. CONCLUSION: The study showed that the percentage of independent patients is significantly reduced when we evaluated the patients by the FIM. In addition, there are some differences in the clinical background that led to a good outcome between that evaluated by mRS and FIM.

Necessity for surveillance for hepatocellualr carcinoma in older patients with chronic hepatitis C who achieved sustained virological response.

Background and Aim: Hepatocellular carcinoma (HCC) surveillance in low-risk patients (annual incidence <1.5%) is not recommended per the American Association for the Study of Liver Diseases guidelines. Because patients with chronic hepatitis C with non-advanced fibrosis who have achieved sustained virological response (SVR) have a low risk of HCC, HCC surveillance is not recommended for them. However, aging is a risk factor for HCC; threfore, the necessity for HCC surveillance in older patients with non-advanced fibrosis needs to be verified. Methods: This multicenter, prospective study enrolled 4993 patients with SVR (1998 patients with advanced fibrosis and 2995 patients with non-advanced fibrosis). The HCC incidence was examined with particular attention to age. Results: The 3-year incidence of HCC in patients with advanced and non-advanced fibrosis was 9.2% (95% CI: 7.8-10.9) and 2.9% (95% CI: 2.1-3.7), respectively. HCC incidence was significantly higher in patients with advanced fibrosis (P < 0.001). HCC incidence stratified by age and sex was investigated in patients with non-advanced fibrosis. The HCC incidence in the 18-49, 50s, 60s, 70s, and ≥80 age groups were 0.26, 1.3, 1.8, 1.7, and 2.9 per 100 person-years in men, and 0.00, 0.32, 0.58, 0.49, and 0.57 per 100 person-years in women, respectively. Conclusions: Male patients with non-advanced fibrosis aged ≥60 years have a higher risk of developing HCC and, thus, require HCC surveillance.

Optimal dose period for indisetron tablets for preventing chemotherapy-induced nausea and vomiting with modified FOLFOX6: a randomized pilot study.

BACKGROUND: Indisetron is a serotonin (5-hydroxytryptamine type 3) receptor antagonist that also antagonizes 5-hydroxytryptamine type 4 receptors. We designed a pilot study in order to explore the optimal dosing period for indisetron during modified FOLFOX6 (mFOLFOX6). PATIENTS AND METHODS: Forty-two chemotherapy-naive patients with advanced colorectal cancer scheduled to receive mFOLFOX6 were randomly assigned to either a 1- or 3-day indisetron regimen arm. The primary endpoint was complete protection from vomiting. RESULTS: Proportions of patients with complete protection from vomiting were 85.7% [95% confidence interval (CI) 63.7-97.0] with the 3-day regimen and 81.0% (95% CI 58.1-94.6) with the 1-day regimen. Proportions of patients with complete protection from nausea were 47.6% in each arm (95% CI 25.7-70.2). No rescue therapy rates were 66.7% (95% CI 43.0-85.4) versus 57.1% (95% CI 34.0-78.2). No severe adverse events were observed in either arm. CONCLUSION: Both 1- and 3-day indisetron regimens were feasible for preventing nausea and vomiting induced by mFOLFOX6.

Phase II study of combined treatment with irinotecan and S-1 (IRIS) in patients with inoperable or recurrent advanced colorectal cancer (HGCSG0302).

OBJECTIVES: This phase II study was designed to evaluate the efficacy and safety of oral fluoropyrimidine S-1 plus irinotecan (IRIS regimen) in patients with previously untreated metastatic colorectal cancer. METHODS: The response rate was the primary endpoint. Safety, progression-free survival time, and median survival time were secondary endpoints. The subjects were untreated patients with inoperable advanced colorectal cancer. Irinotecan was administered at a dose of 100 mg/m² (on days 1 and 15). S-1 (40 mg/m²) was administered for 2 weeks (on days 1 to 14) and followed by a 2-week rest. RESULTS: Forty patients were enrolled. Four patients had grade 4 neutropenia, and six patients had grade 3 diarrhea. No other serious hematologic or nonhematologic adverse reactions occurred, and all patients received IRIS safely on an outpatient basis. The response rate was 52.5% (95% confidence interval [CI], 36.1-68.5%). Median progression-free survival was 8.6 months (95% CI, 5.3-11.9), and median survival time was 23.4 months (95% CI, 15.9-30.8). CONCLUSIONS: IRIS produced a high response rate and could be given safely. IRIS may become a first-line treatment for inoperable or recurrent advanced colorectal cancer.

[A case of diverticular form type of congenital choledochal dilatation with anomalous arrangement of pancreaticobiliary duct].

We report a case of diverticular form type of congenital choledochal dilatation with anomalous arrangement of pancreaticobiliary duct and bile duct stone. The patient was a 63-year-old woman with the chief complaint of epigastralgia. Abdominal CT showed low density area suggesting cystic lesion at the region of pancreatic head. MRCP and ERCP revealed dilatation of the common bile duct in the multiple diverticular form with anomalous arrangement of pancreaticobiliary duct. A 2.0cm sized stone was also recognized in the dilated common bile duct. The patient underwent resection of gall bladder and dilated common bile duct, followed by hepatico-jejunostomy. Histological findings did not revealed malignant changes in the mucosa of both gall bladder and dilated common bile duct.

A Prospective Multicenter Study Evaluating Bleeding Risk after Endoscopic Ultrasound-Guided Fine Needle Aspiration in Patients Prescribed Antithrombotic Agents.

BACKGROUND/AIMS: Although the risk of bleeding after endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is low, the safety of EUS-FNA in patients prescribed antithrombotic agents is unclear. Therefore, this study evaluated the incidence of bleeding after EUS-FNA in those patients. METHODS: Between September 2012 and September 2015, patients who were prescribed antithrombotic agents underwent EUS-FNA at 13 institutions in Japan were prospectively enrolled in the study. The antithrombotic agents were managed according to the guidelines of the Japanese Gastrointestinal Endoscopy Society. The rate of bleeding events, thromboembolic events and other complications within 2 weeks after EUS-FNA were analyzed. RESULTS: Of the 2,629 patients who underwent EUS-FNA during the study period, 85 (62 males; median age, 74 years) patients were included in this stduy. Two patients (2.4%; 95% confidence interval [CI], 0.6% to 8.3%) experienced bleeding events. One patient required surgical intervention for hemothorax 5 hours after EUS-FNA, and the other experienced melena 8 days after EUS-FNA and required red blood cell transfusions. No thromboembolic events occurred (0%; 95% CI, 0.0% to 4.4%). Three patients (3.5%; 95% CI, 1.2% to 10.0%) experienced peri-puncture abscess formation. CONCLUSIONS: The rate of bleeding after EUS-FNA in patients prescribed antithrombotic agents might be considerable.

[A case of granulocyte-colony stimulating factor producing ductal adenocarcinoma of the pancreas].

We report a case of pancreatic ductal adenocarcinoma producing granulocyte-colony stimulating factor (G-CSF). A 56-year-old Japanese man was admitted to our hospital with back pain and high fever. An abdominal CT scan revealed masses in the pancreatic body to the tail, and both lobes of the liver. A biopsy specimen of the hepatic tumor demonstrated metastatic poorly differentiated adenocarcinoma. We administered oral S-1 in combination with gemcitabine. However, his general condition gradually worsened, and a high serum level of G-CSF persisted. He died 135 days after admission. The diagnosis of autopsy was pancreatic ductal adenocarcinoma. Immunohistochemical staining showed the presence of G-CSF in tumor cells. The final diagnosis was G-CSF-producing pancreatic carcinoma.

Severe hypercalcemia associated with hepatocellular carcinoma secreting intact parathyroid hormone: a case report.

Here we describe a 73-year-old woman with hypercalcemia caused by a hepatocellular carcinoma (HCC) secreting intact parathyroid hormone (iPTH). Serum tumor markers and dynamic CT findings indicated a diagnosis of HCC. The source of the elevated serum iPTH was not obvious. Transarterial chemoembolization (TACE) was effective against the HCC, and the serum iPTH level fell to within the normal range, suggesting a correlation between the carcinoma and the iPTH. About 2 months later, the tumor had grown and the serum calcium level increased leading to physical deterioration and death. This clinical course suggested that HCC can ectopically secrete iPTH.