Chemotherapy, host response and molecular dynamics in periampullary cancer: the CHAMP study.

BACKGROUND: Pancreatic cancer is a devastating disease with a dismal prognosis. Despite profound medical advances in systemic therapies for other types of aggressive tumours during recent years, a diagnosis of pancreatic cancer is still often synonymous with a fatal outcome. The term periampullary cancer includes pancreatic cancer and applies to the group of tumours found in proximity to the ampulla of Vater. Molecular events and immune response in the host during chemotherapy remain largely unexplored in this group of tumours. Therefore, the "Chemotherapy, Host Response and Molecular Dynamics in Periampullary Cancer (CHAMP)" study aims to monitor these processes to gain new insight into this perplexing disease. METHODS: The CHAMP study is a prospective, single-arm observational study. All patients diagnosed with pancreatic or other periampullary adenocarcinoma undergoing adjuvant or palliative chemotherapy treatment in the Department of Oncology, Skåne University Hospital, are invited to participate. Clinical and pathological data will be compiled at study entry. A single tissue microarray (TMA) block is constructed for each patient with a resected tumour and blood samples are drawn before, during and after chemotherapy in order to sample peripheral blood mononuclear cells (PBMC), cytokines and circulating tumour DNA (ctDNA). Next generation sequencing will be performed on tumour tissue and ctDNA to detect changes in the clonal landscape over space and time. DISCUSSION: Despite the recent emergence of some promising biomarkers for periampullary cancer, there has been a lack of success in clinical implementation. Cancer cells continuously adapt and become resistant to treatment during chemotherapy. To be able to keep pace with and hopefully overtake this rapid evolution we must, with the help of new diagnostic tools, be ready to adapt and alter treatment accordingly. It seems to us that the only way forward is to gain a better understanding of the dynamics of the disease during treatment. With insights gained from the CHAMP study we hope to find answers to key questions in this largely unexplored territory. TRIAL REGISTRATION: This study has been registered 30th October 2018 at clinicaltrials.gov as NCT03724994.

Transient High Pressure in Pancreatic Ducts Promotes Inflammation and Alters Tight Junctions via Calcineurin Signaling in Mice.

BACKGROUND & AIMS: Pancreatitis after endoscopic retrograde cholangiopancreatography (PEP) is thought to be provoked by pancreatic ductal hypertension, via unknown mechanisms. We investigated the effects of hydrostatic pressures on the development of pancreatitis in mice. METHODS: We performed studies with Swiss Webster mice, B6129 mice (controls), and B6129 mice with disruption of the protein phosphatase 3, catalytic subunit, ßisoform gene (Cnab-/- mice). Acute pancreatitis was induced in mice by retrograde biliopancreatic ductal or intraductal infusion of saline with a constant hydrostatic pressure while the proximal common bile duct was clamped -these mice were used as a model of PEP. Some mice were given pancreatic infusions of adeno-associated virus 6-nuclear factor of activated T-cells-luciferase to monitor calcineurin activity or the calcineurin inhibitor FK506. Blood samples and pancreas were collected at 6 and 24 hours and analyzed by enzyme-linked immunosorbent assay, histology, immunohistochemistry, or fluorescence microscopy. Ca2+ signaling and mitochondrial permeability were measured in pancreatic acinar cells isolated 15 minutes after PEP induction. Ca2+-activated phosphatase calcineurin within the pancreas was tracked in vivo over 24 hours. RESULTS: Intraductal pressures of up to 130 mm Hg were observed in the previously reported model of PEP; we found that application of hydrostatic pressures of 100 and 150 mm Hg for 10 minutes consistently induced pancreatitis. Pancreatic tissues had markers of inflammation (increased levels of interleukin [IL] 6, IL1B, and tumor necrosis factor), activation of signal transducer and activator of transcription 3, increased serum amylase and IL6, and loss of tight junction integrity. Transiently high pressures dysregulated Ca2+ processing (reduced Ca2+ oscillations and an increased peak plateau Ca2+ signal) and reduced the mitochondrial membrane potential. We observed activation of pancreatic calcineurin in the pancreas in mice. Cnab-/- mice, which lack the catalytic subunit of calcineurin, and mice given FK506 did not develop pressure-induced pancreatic inflammation, edema, or loss of tight junction integrity. CONCLUSIONS: Transient high ductal pressure produces pancreatic inflammation and loss of tight junction integrity in a mouse model of PEP. These processes require calcineurin signaling. Calcineurin inhibitors might be used to prevent acute pancreatitis that results from obstruction.

Prognostic effect of hENT1, dCK and HuR expression by morphological type in periampullary adenocarcinoma, including pancreatic cancer.

BACKGROUND: Putative biomarkers of gemcitabine response have been extensively studied in pancreatic cancer, but less so in other types of periampullary adenocarcinoma. The most studied biomarker is human equilibrative nucleoside transporter 1 (hENT1), and the activating enzyme deoxycytidine kinase (dCK) has also been linked to treatment response. The RNA-binding protein human antigen R (HuR) has been demonstrated to confer increased dCK levels in vitro and to predict gemcitabine response in vivo. Here, we investigated the prognostic impact of hENT1, dCK and HuR in pancreatobiliary (PB) and intestinal (I) type periampullary cancers, respectively. MATERIAL AND METHODS: Immunohistochemical expression of hENT1, dCK and HuR was evaluated in tissue microarrays with all primary tumours and 103 paired lymph node metastases from a consecutive retrospective cohort of 175 patients with resected periampullary adenocarcinomas. RESULTS: In patients with PB-type tumours, neither hENT1 nor dCK expression was prognostic. A high HuR cytoplasmic/nuclear ratio was associated with a significantly reduced five-year overall survival (OS) in patients receiving adjuvant gemcitabine (HR 2.07, 95% CI 1.03-4.17) but not in untreated patients (pinteraction = 0.028). In patients with I-type tumours receiving adjuvant chemotherapy, high dCK expression was significantly associated with a prolonged recurrence-free survival (RFS) (HR 0.09, 95% CI 0.01-0.73, pinteraction = 0.023). Furthermore, HuR expression was associated with a prolonged OS and RFS in unadjusted but not in adjusted analysis and hENT1 expression was an independent predictor of a prolonged RFS (HR 0.24, 95% CI 0.10-0.59), regardless of adjuvant treatment. CONCLUSION: hENT1 expression is a favourable prognostic factor in I-type, but not in PB-type tumours. High dCK expression is a favourable prognostic factor in patients with I-type tumours receiving adjuvant treatment and a high cytoplasmic/nuclear HuR ratio is a negative prognostic factor in gemcitabine-treated PB-type tumours. Morphological subtype should always be considered in biomarker studies on periampullary cancer.

Advances in Molecular Pathology and Treatment of Periampullary Cancers.

OBJECTIVES: Periampullary cancers (PACs) include the following 4 traditional anatomic subtypes: pancreatic, ampullary, biliary, or duodenal cancers. This review was performed to highlight recent advances in the genomic and molecular understanding of each PAC subtype and the advances in chemotherapeutic and molecular trials in these cancer subtypes. RESULTS: Recent advances have highlighted differences in the genomic and molecular features within each PAC subtype. Ampullary cancers can now be further defined accurately into their intestinal and pancreatobiliary subtypes using histomolecular profiling. K-ras mutation, which occurs in most pancreatic cancers, is found to occur less frequently in ampullary (42%-52%), biliary (22%-23%), and duodenal cancers (32%-35%), suggesting crucial differences in targetable mutations in these cancer subtypes.Ampullary cancers of intestinal subtype and duodenal cancers seem to share similarities with colorectal cancer, given that they respond to similar chemotherapeutic regimens. This has potential implications for clinical trials and treatment selection, where PACs are often considered together. CONCLUSIONS: Future trials should be designed in view of our increased understanding of the different anatomic and histomolecularly profiled subtypes of PAC cancers, which respects their individual molecular characteristics, phenotype, and response to treatment.

Adjuvant chemoradiotherapy in periampullary cancers--Where does it stand with conformal radiotherapy: A single institution experience.

BACKGROUND: Treatment of periampullary cancer involves Whipple surgery, followed by adjuvant radiotherapy and chemotherapy. Postoperative radiotherapy is particularly useful in managing high-risk patients (tumors involving the pancreas, poorly differentiated histology, involved lymph nodes and positive margins). Here, we review our results of treatment of 84 patients treated by surgery and adjuvant radiotherapy and chemotherapy. MATERIAL AND METHODS: A retrospective analysis of 84 patients of periampullary cancers treated in our department between January 2007 and December 2012 was carried out. All patients underwent Whipples surgery followed by postoperative radiotherapy 45-50 Gy/25-28 number in those presenting with high-risk features. Radiotherapy was delivered using three-dimensional conformal technique with 6 MV photons using three field treatment plans. Chemotherapy was given for 6 cycles using gemcitabine and oxaliplatin regimen repeated 2 weekly. RESULTS: Eighty four postoperative patients with high-risk features were available for the final analysis. There were 69 males and 15 female patients. There were 34.5% stage I, 57.1% stage II and 8.3% stage III patients. At end of adjuvant treatment with radiotherapy and chemotherapy 70% patients had a complete response, 7.5% had residual disease, 15% showed progressive disease, 5% were dead and 2.5% defaulted the treatment. The mean number of chemotherapy cycles received was 2.6. At 1 year follow-up the probability of disease free survival was 80% for node-negative patients versus 73% for node-positive disease (P = 0.27). Patients with stage up to IIA had a 1 year disease free survival of 83% versus 40% for patients with stage beyond IIA (P = 0.024). CONCLUSIONS: Our results showed a trend favoring lymph node negative status with disease free survival. With computed tomography based planning, adequate delineation of draining nodes is possible, and radiation toxicity has significantly decreased. Adequate coverage of nodal basins during radiotherapy planning is important, and stage of the disease seems to be an important prognostic factor.

The role of 64-slice CT following perfusion with iohexol via the hepatopancreatic ampulla in assessing pancreaticobiliary junctions.

The aim of this study was to delineate the structure of the pancreatic and biliary ducts in premature infants using a novel imaging method. The duodenal papillae of 30 premature infant cadavers were dissected. The pancreatic and biliary ducts were visualized using 64-detector multislice spiral computed tomography (MSCT). Contrast agent was injected into the duodenal papilla via the hepatopancreatic ampulla of Vater. MSCT scanning revealed both the pancreatic and biliary ducts as well as the common channel in 18 cases. The bile duct was visualized in the remaining 12 cases. Four patterns of the pancreaticobiliary ductal junction were noted: Y-type (73.3%), U-type (13.3%), V-type (6.7%), and II-type (6.7%). The results showed that MSCT and three-dimensional reconstruction can be used to visualize the junction pattern and common channel of the pancreatic and biliary ducts, and the structure of the surrounding tissue, in premature infants.

Direct spraying of shakuyakukanzoto onto the duodenal papilla: a novel method for preventing pancreatitis following endoscopic retrograde cholangiopancreatography.

BACKGROUND/AIMS: Topical epinephrine application to the duodenal papilla reduces spasm of the sphincter of Oddi and prevents acute pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP). Shakuyakukanzoto (TJ-68) has an inhibitory effect on muscle contraction. Therefore, TJ-68 potentially allows the relaxation of the sphincter of Oddi, which can aid in the prevention of post-ERCP pancreatitis. METHODS: Thirty-six patients planned for ERCP were divided into TJ-68 (n = 17) and control groups (n = 19). In the TJ-68 group, the TJ-68 solution was endoscopically sprayed directly onto the duodenal papilla of patients. To assess the effects of TJ-68, serum amylase levels were measured at 1 h and 1 day after ERCP and symptoms were evaluated. RESULTS: The serum amylase levels at 1 h after ERCP were 273.6 ± 212.0 IU/l in the TJ-68 group and 428.7 ± 281.6 IU/l in the control group, showing a statistically significant difference (p = 0.036). The serum amylase levels at 24 h after ERCP were 230.0 ± 182.7 IU/l in the TJ-68 group and 497.4 ± 514.0 IU/l in the control group (p = 0.011). Post-ERCP pancreatitis was observed in 0 and 4 patients (21.1%) in the TJ-68 and control groups, respectively, which was not statistically significant (p = 0.11). CONCLUSION: Direct TJ-68 solution application to the duodenal papilla significantly inhibited the elevation of serum amylase levels. However, the preventive effect regarding post-ERCP pancreatitis was not confirmed in this study.

Lethal cardiotoxicity, steatohepatitis, chronic pancreatitis, and acute enteritis induced by capecitabine and oxaliplatin in a 36-year-old woman.

A 36-year-old female was hospitalized with symptoms suggesting intestinal occlusion. She was diagnosed with adenocarcinoma of the ampulla of Vater (pT4N0 stage) and underwent cephalic duodenopancreatectomy 8 months ago. Five cycles of postoperative chemotherapy were administrated using capecitabine and oxaliplatin (CAPOX or XELOX), the last one being completed 1 month ago. During the present hospitalization, because of normal computed tomography and ultrasound abdominal examination, rehydration and antibiotherapy were administrated. However, 4 days after hospital admission, the patient died. At autopsy and histological examination, we found a severe myocardial sclerosis with large scarring areas, severe steatohepatitis, chronic pancreatitis with large fibrotic areas, and acute enteritis. Alcohol consumption was denied. The patient died due to associated heart, liver and pancreatic failure. This multiorgan toxicity and death following CAPOX regimen had not yet been reported in the literature. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6472150549833105.

Proton therapy with concomitant capecitabine for pancreatic and ampullary cancers is associated with a low incidence of gastrointestinal toxicity.

BACKGROUND: To review treatment toxicity for patients with pancreatic and ampullary cancer treated with proton therapy at our institution. MATERIAL AND METHODS: From March 2009 through April 2012, 22 patients were treated with proton therapy and concomitant capecitabine (1000 mg PO twice daily) for resected (n = 5); marginally resectable (n = 5); and unresectable/inoperable (n = 12) biopsy-proven pancreatic and ampullary adenocarcinoma. Two patients with unresectable disease were excluded from the analysis for reasons unrelated to treatment. Proton doses ranged from 50.40 cobalt gray equivalent (CGE) to 59.40 CGE. RESULTS: Median follow-up for all patients was 11 (range 5-36) months. No patient demonstrated any grade 3 toxicity during treatment or during the follow-up period. Grade 2 gastrointestinal toxicities occurred in three patients, consisting of vomiting (n = 3); and diarrhea (n = 2). Median weight loss during treatment was 1.3 kg (1.75% of body weight). Chemotherapy was well-tolerated with a median 99% of the prescribed doses delivered. Percentage weight loss was reduced (p = 0.0390) and grade 2 gastrointestinal toxicity was eliminated (p = 0.0009) in patients treated with plans that avoided anterior and left lateral fields which were associated with reduced small bowel and gastric exposure. DISCUSSION: Proton therapy may allow for significant sparing of the small bowel and stomach and is associated with a low rate of gastrointestinal toxicity. Although long-term follow-up will be needed to assess efficacy, we believe that the favorable toxicity profile associated with proton therapy may allow for radiotherapy dose escalation, chemotherapy intensification, and possibly increased acceptance of preoperative radiotherapy for patients with resectable or marginally resectable disease.

Large cell neuroendocrine carcinoma of the ampulla of Vater.

CONTEXT: Large cell neuroendocrine carcinomas of the ampulla of Vater are rare and confer a very poor prognosis despite aggressive therapy. There are few case reports of large cell neuroendocrine carcinomas of the ampulla of Vater in the literature and to date no studies have been done to establish optimal management. We describe a pooled case series from published reports of neuroendocrine carcinomas of the ampulla of Vater including a case which presented to our institution. METHODS: A narrative review was undertaken including all published English case reports of large cell neuroendocrine carcinomas of the ampulla of Vater. Our primary outcome was to determine the overall survival. RESULTS: Twenty cases of large cell neuroendocrine carcinomas of the ampulla of Vater were identified. Seventy-six percent of patients were reported to have died of disease with a mean survival of 11.8 months. Twenty percent of the tumours were associated with an adenoma. The approximate median survivals were 15 months for those with an associated adenoma and 11 months without. CONCLUSIONS: This pooled analysis demonstrates both the rarity and poor prognosis of large cell neuroendocrine carcinomas of the ampulla of Vater. Although surgical resection is the mainstay of treatment, we review common adjuvant chemotherapy regimes. Prognosis may be improved when these tumours are associated with adenomas, however, further studies are needed.

Ampullary and periampullary tumors: translational efforts to meet a challenge in diagnosis and treatment. Highlights from the "2011 ASCO Gastrointestinal Cancers Symposium". San Francisco, CA, USA. January 20-22, 2011.

Ampullary adenocarcinoma is a rare diagnosis and often managed as carcinomas of pancreatobiliary origin. However, there is accumulating evidence unveiling attributes of ampullary carcinomas that are distinct from that of pancreas or biliary cancers. Growing translational efforts in understanding this rare disease are exemplified by Abstracts #161 and #204 presented at the 2011 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium.

Prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis by epinephrine sprayed on the papilla.

BACKGROUND AND AIM: Epinephrine sprayed on the papilla may reduce papillary edema and prevent acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study was to evaluate the effects of localized irrigation with epinephrine saline for prevention of post-ERCP pancreatitis (PEP). METHODS: A total of 941 patients who were scheduled for ERCP were recruited into this study. We randomized the patients to have 20 mL of either 0.02% epinephrine or saline sprayed on the papilla after diagnostic ERCP to prevent post-ERCP pancreatitis. We recorded duct visualization, presence of pancreatic acinarization, number of injections into the pancreatic duct, total volume of contrast used, and procedure duration. The serum amylase levels were measured at 6, 24 and 48 h after ERCP. We counted the patients of PEPs and compared whether there was significant difference between the pancreatitis group and the no pancreatitis group. RESULTS: A univariate analysis of the explanatory variables between the epinephrine and control groups, the pancreatitis and no pancreatitis groups revealed the treatment to be effective, but most of the groups were not statistically significant. PEPs occurred in 40 of the 941 patients (4.25%), the incidence of pancreatitis tended to be higher in the control group (31/480, 6.45%) than in the epinephrine group (9/461, 1.95%) (P = 0.0086). CONCLUSIONS: Epinephrine sprayed on the papilla may be effective to prevent PEP. Female patients (aged ≥ 18 years and < 35 years) (7/40, 17.5%), common bile duct diameter < 10 mm (27/40, 67.5%), previous cholangitis (3/40, 7.5%), body mass index ≥ 24 (22/40, 55%), and/or serum triglycerides ≥ 5.65 mmol/L (6/40, 15%), might be risk factors for post-ERCP pancreatitis, but are not statistically significant in the study.

[Does the use of fentanyl make Vater's ampulla cannulation difficult? A prospective and comparative study]. / ¿Dificulta la canulación del ámpula de Vater el uso de fentanilo? Un estudio prospectivo y comparativo.

BACKGROUND: Fentanyl is a synthetic opioid with excellent results in perioperative analgesia. It is commonly used for proximal and distal gastrointestinal endoscopic procedures, but its contracting action on the sphincter of Oddi, similar to that of morphine, makes its use for endoscopic cholangiopancreatography (ERCP) controversial. OBJECTIVE: To determinate if intravenous fentanyl as part of deep sedation hinders the cannulation of Vater's papilla during ERCP. MATERIAL AND METHODS: Prospective, comparative, randomized and double-blind trial that enrolled patients undergoing ERCP in 2008, > 18 years old, without previous endoscopic or surgical procedures related with Vater s papilla. Patients were randomized into two groups: patients in whom ERCP was performed with intravenous propofol (group A), and patients in whom the procedure was performed with intravenous fentanyl and propofol (group B). Gender, age, comorbid conditions, reasons for referral, difficulty of cannulation, diagnosis, therapeutic procedures, procedure time and endoscopic complications were all documented. RESULTS: 432 were included: 214 in group A and 218 in group B. Both groups were similar in relation with demographic characteristics, time of sedation and endoscopic procedure. Difficulty in cannulation had not a statistical significance (p = 0.163). The administered dose of propofol were less for group B (p < 0.001). No procedure-related mortality was documented. CONCLUSION: The combination of fentanyl and propofol may be used during ERCP, since it does not hinder the cannulation of Vater's papilla.

The efficacy of frontline platinum-based combination chemotherapy in advanced adenocarcinoma of the ampulla of Vater.

Adenocarcinoma arising from the ampulla of Vater is a rare neoplasm that accounts for only 0.2% of all gastrointestinal tract malignancies and has limited data regarding its frontline therapy. We investigated the treatment outcomes in patients with advanced adenocarcinoma of the ampulla of Vater receiving frontline cisplatin-based combination chemotherapy. We analyzed 29 patients with advanced adenocarcinoma of the ampulla of Vater who had been treated by frontline cisplatin-based combination chemotherapy between June 2003 and April 2008. The chemotherapeutic agent added to cisplatin was gemcitabine in 9 patients and fluorouracil (FU) in 20 patients (11; intravenous 5-FU and 9; oral 5-FU (capecitabine)). The median age of patients was 56 years (range, 36-78), and the median ECOG performance status was 1 (0-1). The confirmed overall response rate was 27.5%, and the disease control rate was 72.4%. In all patients, no complete responses and 8 partial responses were observed (overall response rate, 27.5%). Stable disease was observed in 13 patients (44.8%), and progressive disease in 5 patients (17.2%). The median time to progression (TTP) was 4.9 months (95% CI, 3.4-6.4), and the median overall survival (OS) was 12.5 months (95% CI, 10.6-14.4). There were no significant differences for TTP and OS according to the different chemotherapeutic agents added to cisplatin. Grade 3 or 4 hematologic toxicities included leukopenia in seven patients and thrombocytopenia in one patient. There were no grade 3 or 4 nonhematologic toxicities or treatment-related deaths. The cisplatin-based combination chemotherapy showed moderate activity and a favorable toxicity profile as a frontline treatment for patients with advanced adenocarcinoma of the ampulla of Vater.

Epinephrine sprayed on the papilla for prevention of post-ERCP pancreatitis.

BACKGROUND: Epinephrine sprayed on the papilla may reduce papillary edema and thus prevent acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study was to determine the efficacy of this technique for prevention of post- ERCP pancreatitis. METHODS: Patients scheduled for ERCP were recruited into this study. We randomized the patients to have 10 ml of either 0.02% epinephrine (epinephrine group) or saline (control group) sprayed on the papilla after diagnostic ERCP and prospectively analyzed the occurrence of post-ERCP pancreatitis between the groups. We recorded duct visualization, presence of pancreatic acinarization, number of injections into the pancreatic duct, total volume of contrast used, and procedure duration. RESULTS: There was no significant difference between the groups with regard to visualization of the bile duct and/or the main and accessory pancreatic ducts, presence of pancreatic acinarization, number of injections into the pancreatic duct, total volume of contrast used, and procedure duration. Overall, post-ERCP pancreatitis occurred in 4 of the 370 patients (1.1%). The incidence of pancreatitis tended to be higher in the control group (4/185) than in the epinephrine group (0/185) (P = 0.1230). CONCLUSIONS: Epinephrine sprayed on the papilla tended to prevent post-ERCP pancreatitis, although it was not statistically significant because of the low incidence of pancreatitis. Further studies on the efficacy of this technique in patients at high risk for pancreatitis, and on other volumes and/or concentrations of epinephrine, are warranted.

Confirmation of the antispasmodic effect of shakuyaku-kanzo-to (TJ-68), a Chinese herbal medicine, on the duodenal wall by direct spraying during endoscopic retrograde cholangiopancreatography.

The purpose of the study was to evaluate the suppressive effect of TJ-68 on duodenal spasms during endoscopic retrograde cholangiopancreatography (ERCP). At the point when the duodenal papilla was confirmed after insertion of the endoscope during ERCP, 5.0 g TJ-68 (Tsumura Co., Tokyo, Japan) was dissolved in 50 ml of saline at 36 degrees C, and the whole volume was sprayed slowly using a spray tube from the orifice of the forceps to the duodenal papilla of the 50 patients who demonstrated peristalsis of the digestive tract ("duodenal spasm"). The endoscopic procedure was not performed during that time, and the time until the spasm was suppressed was determined. After the arrest of the spasm, the intended tests and treatment were conducted, and the time until the duodenal spasm started again was determined. The suppressive effect on duodenal spasm was observed in 38 (76%) of 50 patients. The duration from the spraying of TJ-68 of the patients who observed the suppressive effect on duodenal spasm was 50-182 s (mean 122 +/- 21 s). The spasm arrest duration was 7.2-21 min (mean 9.6 +/- 1.2 min). Direct spraying of TJ-68 on the duodenal mucosa suppressed duodenal spasm, and it may be useful during ERCP when anticholinergic agents are contraindicated.

Adjuvant chemo-radiotherapy in ampullary cancers.

PURPOSE: Patterns of failure following surgical treatment of ampullary cancers indicate that up to 45% of patients develop loco-regional recurrence. The effect of adjuvant chemo-radiotherapy on survival and loco-regional control is not yet established in this malignancy. PATIENTS AND METHODS: From January 1989 to December 2000, 113 patients underwent pancreatico-duodenectomy for ampullary cancer. One hundred and four patients who survived the operation were available for analysis to study the effect of adjuvant chemo-radiotherapy on survival and loco-regional control. Forty-nine patients received adjuvant chemo-radiotherapy (median dose 50.4 Gy with concurrent 5-Flurouracil) and long-term outcome in these patients was compared with those 55 who did not receive adjuvant therapy. RESULTS: The overall median survival was 30.1 (range 1.6-140.0) months with actuarial 1, 3 and 5-year survival rates of 79, 43 and 33%, respectively. No significant difference in median survival (34.6 vs 24.5 months; P=0.3) and actuarial 5-year survival rates (38 vs 28%) was seen between those who received and those who did not receive adjuvant therapy. Adjuvant chemo-radiotherapy did not influence the survival in high-risk patients (P=0.84), in various T and N stages and had no impact on loco-regional recurrence (P=0.6). CONCLUSIONS: Adjuvant chemo-radiotherapy did not improve the long-term survival or decrease recurrence rates in patients with ampullary cancers who had undergone pancreatico-duodenectomy.

Small follicular lymphoma arising near the ampulla of vater: a distinct subtype of duodenal lymphoma?

A 49-yr-old Japanese woman underwent upper gastrointestinal endoscopy because of nonspecific dyspepsia. Endoscopy revealed a flat elevated lesion about 15 mm in diameter adjacent to the duodenal papilla, the surface of which was uneven and covered with whitish granules. Based on the results of histological examination with immunohistochemistry (positive for CD10, CD20, CD79a, and bcl-2 protein, negative for CD5 and cyclin D1), a diagnosis of grade 1/3 follicular lymphoma was established. Systemic staging examinations suggested the lymphoma was restricted to the mucosa and superficial portion of the submucosa in the duodenal wall. The patient was treated with a combination of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and monoclonal anti-CD20 antibody (rituximab), in addition to radiotherapy. After six courses of this combination chemotherapy, complete regression of the lymphoma was observed. Although reports of small duodenal lymphoma (<20 mm or localized to the mucosa or submucosa) are extremely rare, the features of this case are characteristic of small duodenal lymphoma in terms of evolution around the ampulla of Vater, low-grade follicular type, occurrence in a women, occurrence in the fourth decade of life, and favorable outcome, and this type of tumor may need to be distinguished by pathogenesis and clinical behavior from various other gastrointestinal lymphomas.