Resection of carcinoma in situ and minimally invasive carcinoma of the pancreas in a patient presenting with stenosis and post-stenotic dilatation of the main pancreatic duct on endoscopic ultrasonography and positive serial pancreatic juice aspiration cytology.

We report a rare case of a 67-year-old man who underwent resection of carcinoma in situ and minimally invasive carcinoma of the pancreas. The patient presented with upper abdominal and back pain. No definite pancreatic mass was detected on abdominal ultrasonography, computed tomography, magnetic resonance imaging (MRI), or endoscopic ultrasonography (EUS). However, EUS and MRI demonstrated stenosis of the main pancreatic duct (MPD) in the body and post-stenotic dilatation, resulting in mild dilatation of MPD in the tail. Serial pancreatic juice aspiration cytology after endoscopic nasopancreatic drainage was suggestive of pancreatic adenocarcinoma. Examination of the distal pancreatectomy specimen demonstrated carcinoma in situ in MPD and branches, with multiple intraepithelial neoplastic lesions in the background pancreas and an additional focus of minimally invasive carcinoma.

Synchronous triple cancers of the pancreas, stomach, and cecum treated with S-1 followed by pancrelipase treatment of pancreatic exocrine insufficiency.

CONTEXT: Pancreatic cancer is frequently complicated by malignancies in other organs. However, synchronous triple cancers including pancreatic cancer have been seldom reported in the English language literature. CASE REPORT: We describe the rare case of a 77-year-old man with triple cancers of the pancreas, stomach, and cecum. Biopsies revealed that all three tumors were adenocarcinomas. The pancreatic and gastric tumors were positive for cytokeratin 7 and negative for cytokeratin 20, whereas the cecal tumor was negative for cytokeratin 7 and positive for cytokeratin 20. K-ras mutations were present at codon 12 in the pancreatic tumor and at codon 13 in the cecal tumor, but were absent from the gastric tumor. Since the three tumors had different characteristics, the patient was diagnosed with synchronous triple cancers. Because invasive surgery was required to remove all three tumors and the patient had risk factors for surgery, we elected to treat him with chemotherapy. All three cancers were markedly reduced in size by treatment with cycles of 100 mg/day S-1 for 2 weeks, followed by a 1-week rest. The patient later developed hypoproteinemia and anasarca, which was diagnosed as pancreatic exocrine insufficiency due to pancreatic head cancer. Treatment with pancrelipase resulted in dramatic improvements in hypoproteinemia and anasarca. CONCLUSIONS: This is the first case report in which S-1 was effective in triple cancers of the pancreas, stomach, and cecum. Patients with pancreatic head cancer should be monitored for pancreatic exocrine insufficiency.

Multiple factors influencing the release of hTERT mRNA from pancreatic cancer cell lines in in vitro culture.

Since telomerase expression is highly prevalent in human cancers, the quantitation of serum/plasma hTERT (human telomerase reverse transcriptase) mRNA levels may be useful for early detection of PCa (pancreatic cancer). To analyse the correspondence between exhTERT (extracellular hTERT) mRNA levels and hTERT expression, we designed a cell culture system to investigate factors modulating the extracellular levels of hTERT mRNA in media conditioned by eight PCa cell lines. We found that the level of exhTERT mRNA was dependent on cell growth rate. MIAPaCa-2, PANC-1, KLM-1 and PK-9 cells expressed high levels of exhTERT mRNA, independent of cell density, whereas proliferating PK-59, BxPC-3 and PK-45H cells released low levels of exhTERT mRNA. The augmented release of mRNA by spontaneous dead MIAPaCa-2 cells was further increased at postconfluence. In Capan-1 cells, low correspondence of marker was also due to RNase secretion. Upon reaching confluence, some PCa cell lines showed down-regulation of hTERT expression. Following cell-cell adhesion, as shown by E-cadherin engagement, PK-59 cells showed levels of extracellular message below the limits of detection, a loss not due to an increase in message degradation. These results suggest that the levels of exhTERT mRNA in the medium of PCa cell lines are altered not only in response to cell growth rate and cell destruction, but are responsive to extracellular cues such as RNases and cell density. A cell-free assay for exhTERT mRNA may therefore not be useful for early detection of PCa.

Endoscopic findings of upper gastrointestinal lesions in patients with pancreatic cancer.

CONTEXT: Pancreatic cancer is often complicated with upper gastrointestinal lesions. However, there have been few endoscopic studies in pancreatic cancer patients. We retrospectively investigated the upper gastrointestinal lesions in patients with pancreatic cancer who underwent upper gastrointestinal endoscopy. METHODS: Upper gastrointestinal endoscopy was performed in 75 patients with pancreatic cancer between 2003 and 2010. We examined upper gastrointestinal lesions, such as gastroduodenal invasion, ulcers, esophagogastric varices, radiation-induced gastroduodenal mucosal lesions, and portal hypertensive gastropathy. RESULTS: Among the 53 patients with pancreatic cancer who underwent upper gastrointestinal endoscopy at diagnosis, 23 gastrointestinal lesions were observed in 20 patients (38%) as follows: gastroduodenal invasion (n=11), esophagogastric varices (n=7), gastroduodenal ulcers (n=3), portal hypertensive gastropathy (n=1) and duodenal metastasis (n=1). Among the 75 patients with pancreatic cancer, 56 gastrointestinal lesions were identified in 46 patients (61%) during the clinical course as follows: gastroduodenal invasion (n=20), esophagogastric varices (n=14), radiation-induced gastroduodenal mucosal lesions (n=9), gastroduodenal ulcers (except radiation-induced ulcers) (n=8), portal hypertensive gastropathy (n=3), duodenal metastasis (n=1), and gastrointestinal bleeding from unknown primary site (n=1). Twenty-nine (52%) of the 56 gastrointestinal lesions showed symptoms related to the lesions. Fifteen (27%) lesions were accompanied by upper gastrointestinal bleeding. Fourteen (25%) lesions developed according to the progression of pancreatic cancer. CONCLUSION: We should pay attention to upper gastrointestinal lesions in patients with pancreatic cancer.

[Cancer of unknown primary site with epidermal growth factor receptor mutation for which gefitinib proved effective].

We report a 53-year-old man with cancer of an unknown primary site with an epidermal growth factor receptor mutation for which gefitinib was effective. In 2007, he complained of left gluteal pain and right cervical lymph node swelling. He was given a diagnosis of adenocarcinoma at the biopsy of the right cervical lymph node. Although metastases of multiple lymph nodes, bone, and bilateral adrenal glands were found, the primary site could not be determined on close examination, resulting in a diagnosis of cancer of unknown primary site(poor prognosis group). He was then treated with systemic chemotherapy. After he showed resistance to chemotherapy, he received gefitinib as third-line therapy because the tumor harbored an epidermal growth factor receptor(EGFR)mutation. Subsequently, multiple metastatic tumors gradually reduced and clinical benefit was observed for a long time.

[A case of poorly-differentiated neuroendocrine carcinoma of the ascending colon with multiple liver metastases successfully treated with cisplatin and irinotecan].

A 74-year-old woman diagnosed with poorly-differentiated neuroendocrine carcinoma originating from the ascending colon was referred to our hospital. She had felt anorexia, abdominal pains and her (ECOG) performance status was 3. Her CT scan showed that some abdominal lymph nodes were swelling and that there were many metastatic lesions occupying most of the liver. We started chemotherapy with cisplatin and irinotecan according to a regimen for small cell lung cancer. Considering her poor PS, both of the drugs were administered at 30mg/m² twice 4 weeks in the first course of chemotherapy. Her anorexia and abdominal pains immediately disappeared, and CT scan showed that all of the metastases were decreased in size. After 4 courses, however, some of the metastatic lesions were increased in size. She died 8 months after diagnosis. The tumor marker doubling time was 17 days.

[PI3K inhibitor].

PI3K-Akt is an important signal transduction pathway which acts downstream from various growth factor receptors. The PI3K-Akt pathway is activated in many types of cancers by several mechanisms, including growth factor receptor activation, loss of PTEN, and PI3K gene mutations. Therefore, PI3K is thought to be an ideal therapeutic target. A large number of PI3K inhibitors are being developed and evaluated in clinical trials.

Metastatic renal cell carcinoma complicated with diffuse alveolar hemorrhage: a rare adverse effect of sunitinib.

We report the case of a 67-year-old man with metastatic papillary renal cell carcinoma (RCC) who developed bloody sputum after the administration of sunitinib. Chest computed tomography revealed diffuse ground-glass opacity lesions, and bloody bronchoalveolar lavage fluid was obtained by flexible bronchoscopy. The abnormal shadows promptly regressed after withdrawal of sunitinib. In four cycles of sunitinib treatment, he suffered from controllable diffuse alveolar hemorrhage. Finally, he died of respiratory failure 8 months after onset. This is the first case report of diffuse alveolar hemorrhage as an adverse effect of sunitinib in metastatic papillary RCC. Care should be taken with pulmonary hemorrhage in the use of anti-angiogenesis agents in not only squamous cell lung cancer, but also metastatic lung tumors.

[Combined chemotherapy with cisplatin plus vinorelbine showed efficacy in a case of metastatic primary cutaneous adenoid cystic carcinoma].

We report a case of a 65-year-old man with metastatic primary cutaneous adenoid cystic carcinoma that was effectively treated by combination chemotherapy with cisplatin (CDDP) plus vinorelbine(VNR). He detected a tumor mass on the anterior surface of his left patella in 2003 and underwent a tumorectomy in October 2008. He was given a diagnosis of primary cutaneous adenoid cystic carcinoma with metastatic lesions to multiple lungs and left tibial bone and then given chemotherapy combining CDDP plus VNR as the first treatment in December 2008. By this treatment for six cycles, the lung metastatic tumors gradually reduced on chest CT. We reported the efficacy of combined treatment with CDDP plus VNR for primary cutaneous adenoid cystic carcinoma, because this clinical condition was very rare and the standard treatment has still not been established.

Advanced hepatocellular carcinoma treated effectively with irinotecan via hepatic arterial infusion followed by proton beam therapy.

We report a 48-year-old man with hepatocellular carcinoma (HCC) treated with hepatic arterial infusion (HAI) chemotherapy followed by proton beam therapy. The HCC lesion in this patient was 88 mm in diameter, with portal vein tumor thrombosis in the right lobe of the liver. He was first treated with 5-fluorouracil, cisplatin, and isovorin, administered by HAI, combined with interferon-alpha, and he was subsequently treated with epirubicin and mitomycin-C administered by HAI. However, no definite efficacy of either of these treatments was observed. Then, after 3 weeks' continuous administration of irinotecan by HAI, the tumor size decreased to 68 mm in diameter. However, 3 months after reduction of the tumor, the tumor had become enlarged to 100 mm in diameter and intrahepatic metastases were prominent. Angiographic findings indicated that the HCC was fed not only from the right hepatic artery but also from the left gastric and right and left subphrenic arteries. After rearrangement of the arteries, and 3 months' continuous HAI chemotherapy with irinotecan, plus hyperthermia, the tumor size had decreased to 50 mm in diameter. The reduction rate of the main tumor according to the Response Evaluation Criteria in Solid Tumors was 43%; therefore, the efficacy of this treatment was judged as a partial response. Two months after reduction of the tumor, the patient's serum alpha-fetoprotein (AFP) level was elevated, and so docetaxel was administered by HAI instead of irinotecan. The liver tumors showed gradual enlargement during the administration of docetaxel, although the AFP level was suppressed. Proton beam therapy was instituted and the liver tumors showed necrosis after this therapy. The patient died of hepatic failure and distant metastases 6 years after the onset of HCC. As far as we know, this is the first case report of HCC treated effectively with irinotecan administered by HAI followed by proton beam therapy in which tumor suppression and the long-term survival of the patient were observed.

Combined chemotherapy with carboplatin plus irinotecan showed favorable efficacy in a patient with relapsed small cell carcinoma of the prostate complicated with meningeal carcinomatosis.

We report the case of a 65-year-old man with recurrent prostate cancer who presented with meningeal carcinomatosis. In September 2007, he had been diagnosed with mixed type small cell carcinoma and adenocarcinoma at clinical stage T4N1M1 (primary prostate tumor with multiple bone, liver, and lymph node metastases) and hormonal therapy had been administered. Following an increase in the level of pro-gastrin-releasing peptide (ProGRP), combined chemotherapy with cisplatin plus etoposide was implemented and showed efficacy in targeting the small cell carcinoma. In March 2008, he presented with signs of meningeal irritation; his condition deteriorated quickly and multiple brain metastases were confirmed by magnetic resonance imaging (MRI). A sample of cerebrospinal fluid collected by lumbar puncture showed cancer cells and an elevated level of ProGRP. Small cell carcinoma of the prostate complicated with meningeal carcinomatosis was diagnosed. A different chemotherapy regimen was then administered, consisting of a combination of carboplatin plus irinotecan, which is one of the most common first-line treatments for extensive-stage small cell lung carcinoma. From day 20 after the initiation of this therapy, he gradually recovered from the signs of meningeal irritation, and brain MRI showed nearly normal findings; also, the serum level of ProGRP was reduced. In conclusion, we report the efficacy of combined treatment with carboplatin plus irinotecan for small cell carcinoma of the prostate complicated with meningeal carcinomatosis. Because this clinical condition is extremely rare, a gold standard treatment has yet to be established.

A case of pancreatic cancer with formation of a mass mimicking alcoholic or autoimmune pancreatitis in a young man. Possibility of diagnosis by hypermethylation of pure pancreatic juice.

CONTEXT: Mass-forming pancreatitis can be divided into two distinct types: alcoholic and autoimmune. There have been some cases of an ambiguous diagnosis although care was taken to differentiate between alcoholic mass-forming pancreatitis, focal type autoimmune pancreatitis and pancreatic cancer. CASE REPORT: We report a case of pancreatic cancer mimicking alcoholic or autoimmune pancreatitis with the formation of a mass in a 32-year-old man with a history of heavy drinking. Although both serum immunoglobulin G and immunoglobulin G4 levels were normal, many serum auto-antibodies, including the antinuclear antibody, were detected. After he stopped drinking, abdominal computed tomography showed a pancreatic head mass 28 mm in diameter with little and weak enhancement in the early and delayed phases, respectively. Endoscopic retrograde cholangiopancreatography showed an obstruction of the main pancreatic duct in the pancreatic head and marked stenosis of the lower common bile duct. Although a percutaneous ultrasound-guided pancreatic biopsy demonstrated no evidence of autoimmune pancreatitis, he was treated with prednisolone to test the efficacy of steroid therapy. However, the pancreatic mass became enlarged after steroid therapy, and he underwent surgery during which the mass was found to be pancreatic cancer. Although the patient was treated with gemcitabine, he died 5 months after surgery. We retrospectively assessed DNA hypermethylation in the patient's pure pancreatic juice obtained on admission. We observed hypermethylation of the cancer-specific gene tissue factor pathway inhibitor 2 (TFPI2). CONCLUSION: This finding suggests that if the DNA hypermethylation of pure pancreatic juice had been assayed before steroid therapy, it would have supported the diagnosis of pancreatic cancer, and steroid therapy could have been avoided.

[An autopsy case of pancreatic cancer with poor performance status due to peritonitis carcinomatosa treated successfully with continuous infusion of low-dose 5-FU with octreotide].

A 60-year-old man with pancreatic cancer was admitted due to massive ascites in the course of gemcitabine treatment. Cachexic condition progressed due to peritonitis carcinomatosa. Continuous infusion of low dose 5-FU with octreotide was carefully started. Almost all of ascites disappeared after 4 courses of treatment and his general condition markedly improved. This patient died of pneumonia about 13 months after diagnosis of peritonitis carcinomatosa. Autopsy was undergone, and the effect of chemotherapy was confirmed.

A case of autoimmune pancreatitis associated with retroperitoneal fibrosis.

CONTEXT: Autoimmune pancreatitis is characterized by diffuse enlargement of the pancreas, diffuse irregular narrowing of the main pancreatic duct, severe lymphoplasmacytic infiltration and fibrosis of the pancreas. Retroperitoneal fibrosis may occasionally be associated with autoimmune pancreatitis. CASE REPORT: We report a 77-year-old man with autoimmune pancreatitis associated with retroperitoneal fibrosis. Abdominal ultrasonography and computed tomography demonstrated diffuse enlargement of the pancreas and a capsule-like rim. Furthermore, a retroperitoneal mass was recognized anterior to the abdominal aorta. Antinuclear antibody, IgG and IgG4 values were elevated. Therefore, this patient was diagnosed as having autoimmune pancreatitis associated with retroperitoneal fibrosis. We performed steroid therapy using prednisolone. After 4 weeks, both IgG and IgG4 values decreased and both the swelling of the pancreas and also the retroperitoneal mass were obviously diminished. CONCLUSION: This is a rare case of autoimmune pancreatitis associated with retroperitoneal fibrosis.

Preproenkephalin hypermethylation in the pure pancreatic juice compared with p53 mutation in the diagnosis of pancreatic carcinoma.

BACKGROUND: Aberrant methylation of CpG islands is a common mechanism for the dysregulation of tumor suppressor genes in a variety of human malignancies. Preproenkephalin ppENK) hypermethylation is recognized in 90% of pancreatic carcinoma (PCa) tissues, but not in normal pancreas. We analyzed ppENK hypermethylation in pure pancreatic juice (PPJ) in patients with PCa, intraductal papillary mucinous neoplasms (IPMN), and chronic pancreatitis (CP), and elucidated its usefulness as a marker in the diagnosis of PCa compared with p53 mutation. METHODS: PPJ was collected endoscopically from 28 patients with PCa, 15 patients with IPMN, and 20 patients with CP. DNA was extracted from the supernatant and the sediment of PPJ. Methylation-specific polymerase chain reaction was performed for hypermethylation analysis of ppENK. In addition, single-strand conformation polymorphism and direct sequencing were performed simultaneously to identify p53 mutations. RESULTS: The incidence of ppENK hypermethylation in the supernatant and/or the sediment of PPJ was 50% (14 of 28) in patients with PCa. In contrast, the incidence of ppENK hypermethylation was 26.7% (4 of 15) in patients with IPMN, and 5% (1 of 20) in patients with CP (P < 0.002). The incidence of p53 mutations in the PPJ was 42.9% (12 of 28) in patients with PCa and 0% (0 of 20) in patients with CP. Furthermore, the incidence of ppENK hypermethylation and/or p53 mutations in the PPJ was enhanced to 67.9% (19 of 28) in patients with PCa in the combination assay. CONCLUSIONS: These results suggest that ppENK hypermethylation in PPJ is specific for cancer, and the combination assay with p53 enhances the genetic diagnosis of PCa.

Recurrence of renal cell carcinoma diagnosed using contralateral adrenal biopsy with endoscopic ultrasound-guided fine-needle aspiration.

A 76-year-old female in whom a renal cell carcinoma (RCC) lesion was resected 19 years previously presented to our hospital with cognitive dysfunction. Magnetic resonance imaging and computed tomography revealed nodules in the brain, lung, adrenal gland and a pelvic osteolytic lesion. To identify the primary cancer site, the present study performed endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of the left adrenal lesion. Consequently, the pathological findings of the tissue obtained by EUS-FNA were similar to those of the previous nephrectomy specimen, revealing that the adrenal lesion was the recurrence of RCC. The majority of the metastatic lesions in the patient were reduced in size by the multiple kinase inhibitor, pazopanib. Contralateral adrenal metastasis of RCC is rare and the use of EUS-FNA in the diagnosis of adrenal lesions remains to be elucidated. This is a rare case of adrenal lesion, diagnosed by EUS-FNA. Therefore, EUS-FNA is considered to be a useful diagnostic modality of adrenal metastases from unidentified primary tumor types.

Herbal medicine Ninjinyoeito ameliorates ribavirin-induced anemia in chronic hepatitis C: a randomized controlled trial.

AIM: Ribavirin (RBV) shows a strong antiviral effect on hepatitis C virus when used in combination with interferon. However, RBV-induced anemia is a major problem in this therapy. It would be of great clinical importance to ameliorate the anemia without reducing the RBV dose. We report here that, Ninjinyoeito (NYT), a herbal medicine can reduce the RBV-induced anemia. METHODS: Twenty-three patients with chronic hepatitis C were treated with interferon alpha 2b plus RBV with (NYT group) or without (control group) NYT by a randomized selection. Eighteen patients completed the treatment schedule, and hemato-biochemical and virological effects were evaluated. RESULTS: There was no significant difference in biochemical and virological responses between the two groups. However, anemia was significantly reduced in the NYT group compared with the control group. The maximal decrease of Hb in the NYT group (2.59+/-1.10 g/dL) was significantly (P = 0.026) smaller than that in the control group (3.71+/-0.97 g/dL). There was no significant difference in serum glutathione peroxidase activity, serum RBV concentration, and Th1/Th2 balance between the two groups. There was no specific adverse effect in NYT administration. CONCLUSION: These results suggest that NYT could be used as a supportive remedy to reduce the RBV-induced anemia in the treatment of chronic hepatitis C.

Superoxide dismutase is induced during rat pancreatic acinar cell injury.

INTRODUCTION: Free radicals and their scavengers are supposed to be involved in pancreatitis. AIMS: To investigate the expression of superoxide dismutase (SOD) in rat pancreatic acinar cell injury. METHODOLOGY AND RESULTS: As an in vivo model, male WBN/Kob rats were used. Chronic pancreatitis developed spontaneously at 12 weeks in this model and progressed thereafter, but acinar regeneration was recognized at 20 weeks. By semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), manganese SOD (MnSOD) mRNA expression peaked at 8 and 20 weeks, whereas copper/zinc SOD (CuZnSOD) mRNA expression peaked at 12 and 20 weeks. Immunohistochemistry confirmed the localization of SOD in acinar cells. Acinar cell apoptosis peaked at 12 and 20 weeks. In an in vitro study, MnSOD mRNA expression peaked at 2 hours after the addition of arginine to culture medium, whereas apoptosis was increased at 24 hours. CONCLUSION: Thus, the induction of SOD around the onset and at the late stage of chronic pancreatitis in the WBN/Kob rats implies pancreatic ischemia and acinar remodeling, respectively. From the in vitro results, MnSOD expression might reflect a defensive mechanism of acinar cells against oxidative stress or pro-apoptotic stimuli.

Induction of chemokines in rat pancreatic acinar cell injury.

INTRODUCTION: The pathogenesis of chronic pancreatitis (CP), especially of acinar cell injury, is still unclear. Interleukin (IL)-8 is a chemokine that is involved in various inflammatory diseases. AIM: To examine whether IL-8 and other chemokines are expressed in experimental acinar cell injury. METHODOLOGY: IL-8 expression was analyzed in spontaneous CP in the WBN/Kob rat and in rat pancreatic acinar AR4-2J cells treated with various stimuli using reverse transcription-polymerase chain reaction (semiquantitative) and immunohistochemistry. RESULTS: Chronic pancreatitis developed at 12 weeks in the WBN/Kob rats. IL-8, macrophage chemoattractant protein-1, and macrophage inflammatory protein-2 mRNA was expressed from 4 weeks and peaked at 12 weeks. Immunohistochemistry showed a strong expression of IL-8 in acinar cells, proliferating ductular cells, and interstitial infiltrating cells. In contrast, normal pancreatic tissues lacked IL-8 expression. Further, IL-8 mRNA and protein were detectable in AR4-2J cells treated with the various stimuli, such as menadione, tumor necrosis factor-alpha and transforming growth factor beta1. CONCLUSION: These results suggest that IL-8 is expressed in the pancreatic parenchyma and infiltrates in CP and that it plays a role in the initial pathogenesis of CP together with other chemokines and cytokines.

Expression of interleukin-8 in human obstructive pancreatitis.

CONTEXT: Obstructive pancreatitis is a specific form of pancreatitis, which is caused by the obstruction of the main pancreatic duct due to tumors or some other causes. Interleukin-8 is induced in acute pancreatitis, but its expression in obstructive pancreatitis has not been clarified. OBJECTIVE: We attempted to provide some insight into the significance of interleukin -8 in the pathogenesis of pancreatic fibrosis. PATIENTS: Fifteen cases of pancreatic cancer, 7 cases of mucinous cystadenoma, 3 cases of Vater's papilla cancer and 9 normal pancreases were included in this study. MAIN OUTCOME MEASURES: The obstructive pancreatitis portions of the above pathologies were evaluated for interleukin-8 expression by means of immunohistochemistry and in situ hybridization. RESULTS: Interleukin-8 was positive in 72% of cases of obstructive pancreatitis. The positive rate was not significantly related to the etiology of the obstruction (P=0.972). Interleukin-8 was expressed in infiltrating cells, proliferating ductular cells and acinar cells. In contrast, normal pancreases and tumor cells lacked interleukin-8 expression (P<0.001 vs. obstructive pancreatitis). Both immunohistochemistry and in situ hybridization demonstrated that interleukin-8 was expressed mostly in acinar cells in mild pancreatic fibrosis, whereas it was expressed in stromal and ductular cells in moderate and severe pancreatic fibrosis. CONCLUSIONS: These results suggest that interleukin-8 expression is related to the fibrotic process in obstructive pancreatitis.