Pancreatic Head Cancer Research Articles

A duodenal stromal tumor mimicking a pancreatic head tumor: one case report and literature review

Backround Duodenal gastrointestinal stromal tumors are rare tumors. When these tumors arise from the second part of the duodenum they can easily be misdiagnosed as a pancreatic head cancer.

Current Trends in Preoperative Biliary Stenting in Patients With Resected Pancreatic Head Cancer

Current Trends in Preoperative Biliary Stenting in Patients With Resected Pancreatic Head Cancer

Long-term survival after resection of pancreatic ductal adenocarcinoma with para-aortic lymph node metastasis: case report

Pancreatic cancer patients with para-aortic lymph node metastasis have a poor prognosis and patients living longer than 3 years are rare. We had a patient with pancreatic cancer who survived for more than 10 years after removal of the para-aortic lymph node metastasis. A 57-year-old woman was diagnosed with pancreatic head cancer and underwent a pancreaticoduodenectomy with subtotal gastric resection following Whipple reconstruction in 2000. Para-aortic lymph node metastasis was detected during the operation by intraoperative pathological diagnosis and an extended lymphadenectomy was performed with vascular skeletonization of the celiac and superior mesenteric arteries. In 2004, a low-density area was detected around the superior mesenteric artery (SMA) 5 cm from its root and she was treated with gemcitabine, and the area was undetectable after 3 years of treatment. In 2010, computed tomography showed a low-density area around the same lesion with an increased carcinoembryonic antigen level. After 4 months of gemcitabine treatment, we resected the tumor en bloc with the associated superior mesenteric vein and perineural tissue. Histopathological examination of the resected specimen revealed a well-differentiated tubular adenocarcinoma that closely resembled the original primary pancreatic cancer, indicating perineural recurrence 10 years after the initial resection. She had no recurrence around the SMA for more than one year. Although a meta-analysis has not proved the efficacy of preventive radical dissection, this case indicates that a patient with well-differentiated, chemotherapy-responsive pancreatic cancer with para-aortic lymph node metastasis could have a long survival time through extended dissection of the lymph nodes.

Total Laparoscopic Roux-en-Y Cholangiojejunostomy for the Treatment of Biliary Disease

Roux-en-Y cholangiojejunostomy (RCJS) has been widely used in biliary bypass surgeries, but in most reported literature, an assisted miniincision was needed, and studies reporting total laparoscopic Roux-en-Y cholangiojejunostomy (TLRCJS) are rare. The goal of this study was to investigate how to treat hepatic portal bile duct diseases and perform jejunojejunostomy and cholangiojejunostomy totally laparoscopically. We evaluated the feasibility of TLRCJS in treating biliary tract diseases. TLRCJS were performed in 103 patients from January 2000 to August 2011. There were 28 cases of recurrent choledocholithiasis combined with stricture of the common bile duct (CBD) after several stone extractions, 3 patients with iatrogenic bile duct injury, 24 patients with choledochal cyst, 36 patients with hepatic portal cholangiocarcinoma, and 12 patients with cancer of the pancreatic head and periampullary cancer. All surgeries were performed through 5 trocars. First, laparoscopic surgery on the CBD was performed according to the original disease. The CBD was opened and stones were extracted in choledocholithiasis patients. In iatrogenic injury patients, strictured CBD was resected and repaired. Dilated CBD or choledochal cyst with tumor was transected. In patients with malignant jaundice, the CBD was opened longitudinally. At the same time, the bile duct was prepared for cholangiojejunostomy. Second, the positions of the laparoscope and surgeons were altered. The jejunal mesentery and jejunum were transected, and side-to-side jejunojejunostomy (JJS) was performed. The laparoscope and surgeon positions were exchanged again; the Rouxen-Y biliary limb was lifted close to the residual bile duct; and side-to-side or end-to-side choledochojejunostomy (CJS) was performed. Finally, an abdominal drainage tube was placed. All the surgeries were performed successfully. The diameter of the residual bile duct ranged from 0.4 to 3.2 cm (average, 0.9 cm). Three patients had postoperative bile leakage and were treated from 1 week to approximately 1 month with abdominal drainage. Postoperative intraperitoneal hemorrhage and stress ulcer of the stomach occurred in 2 patients with biliary tract injury combined with obstructive jaundice. One with intraperitoneal hemorrhage was cured by another laparoscopic surgery. The other patient was cured after 2 days of abdominal drainage, antacids, and hemostatic drug therapy. The follow-up duration of 95 patients was 4 to 93 months (average, 48.3 months). The follow-up rate was 92.2% (95/103). Patients with cancer died of metastasis or cachexia during 14-month follow-up with no postoperative complication. Reflux cholangitis occurred in 3 patients 2, 3, and 5 years after the operation, respectively. No anastomotic stricture or other complication was found in other patients during the follow-up. TLRCJS is the best and first choice for patients with biliary tract diseases that need biliary-jejunal anastomosis. But it is essential that the surgeon has proficiency in laparoscopic surgeries.

Metachronous colonic metastasis from pancreatic cancer seven years post-pancreatoduodenectomy

Colonic metastasis from other organs is very rare. Here we report the case of a 62-year-old man with a history of pancreatoduodenectomy for stage IIB pancreatic head cancer performed seven years back. He presented with abdominal distension and pain. Under the preoperative diagnosis of bowel obstruction, surgical treatment was performed, and a circumferential lesion causing bowel obstruction of the ascending colon was detected. A right hemicolectomy with lymph node dissection was performed. The specimen showed a 5-cm wall thickening with a cobble-stone like appearance of the ascending colon, which morphologically appeared scirrhous. Histological examination revealed cancer nests invading from the subserosa to the muscular and submucosal layers of the colon. Immunohistochemical analysis of the tumor cells demonstrated positive staining for cytokeratin 7, but negative for cytokeratin 20, which was the same as the previous pancreatic cancer specimen. These pathological and immunohistochemical features strongly supported the diagnosis of colonic metastasis from the pancreas. Thereafter, the patient received systemic chemotherapy, but unfortunately, he died 14 mo after the surgery.

術前化学療法中に十二指腸穿通・出血を来した膵頭部癌の1切除例

症例は66歳の男性で，CTにて腫瘍径3.0 cmの上腸間膜静脈浸潤をともなう膵頭部癌と診断した．上腸間膜動脈神経叢浸潤が疑われたため，術前補助化学療法（GEM+S-1併用療法）を施行する方針とした．1クール終了後に貧血で来院，上部消化管内視鏡検査にて十二指腸穿通部からの出血を認めた．クリッピングとトロンビン散布にて止血が得られたが，抗癌剤による腫瘍変性からの出血を疑い術前化学療法は中止し，止血から6日後に膵頭十二指腸切除術を施行した．病理組織学的検査所見では穿通部に腫瘍細胞の壊死を認め，化学療法の効果によるものと推察された．第24病日に退院し，術後補助化学療法としてGEM単剤の投与を施行したが，再発を来し術後9か月で永眠された．膵癌に対する術前治療が広まりつつあり，今後，本症例のような穿孔・穿通などのoncologic emergency の機会は増加するものと予想される．

膵頭部癌に合併した膵内膿瘍の1切除例

症例は60歳代，男性．主訴は心窩部痛．血液検査にて血清アミラーゼ値の上昇，腹部超音波およびCT検査にて膵頭部に3cm大の腫瘍性病変とその末梢側の主膵管の拡張に加え，膵尾部に2.5cm大の嚢胞性病変を認めた．PET-CT検査では頭尾部各々に有意な異常集積を認めた．膵頭部の病変は針生検にて腺癌と診断した．手術を施行，膵尾部に周囲組織と強く固着した腫瘤性病変を認め，膵尾部癌による直接浸潤が疑われた．膵頭部の腫瘍は門脈浸潤が疑われ，手術は膵全摘，左副腎合併切除，横行結腸部分切除および門脈合併切除を行った．病理組織学検査にて膵頭部の腫瘍は低分化型腺癌と診断された．一方，膵尾部には内部に混濁した液体の貯留を伴う嚢胞性病変とその周囲に高度の炎症性変化が認められたが悪性所見は認められなかった．膵頭部癌に合併した膵尾部膿瘍と診断した．膵癌と膵膿瘍の合併例の報告は少なく自験例に文献的考察を加えて報告する．

Gastrojejunostomy in patients with unresectable pancreatic head cancer - the use of Roux loop significantly shortens the hospital length of stay

To evaluate the use of the Roux loop on the postoperative course in patients submitted for gastroenteroanastomosis (GE). Non-jaundiced patients (n = 41) operated on in the Department of General and Transplant Surgery in Lodz, between January 2010 and December 2011 were enrolled. The tumor was considered unresectable when liver metastases or major vascular involvement were confirmed. Patients were randomized to receive Roux (n = 21) or conventional GE (n = 20) on a prophylactic basis. The mean time to nasogastric tube withdrawal in Roux GE group was shorter (1.4 ± 0.75 vs 2.8 ± 1.1, P < 0.001). Time to starting oral liquids, soft diet and regular diet were decreased (2.3 ± 0.86 vs 3.45 ± 1.19; P < 0.001; 3.3 ± 0.73 vs 4.4 ± 1.23, P < 0.001 and 4.5 ± 0.76 vs 5.6 ± 1.42, P = 0.002; respectively). The Roux GE group had a lower use of prokinetics (10 mg thrice daily for 2.2 ± 1.8 d vs 3.7 ± 2.6 d, P = 0.044; total 62 ± 49 mg vs 111 ± 79 mg, P = 0.025). The mean hospitalization time following Roux GE was shorter (7.7 d vs 9.6 d, P = 0.006). Delayed gastric emptying (DGE) was confirmed in 20% after conventional GE but in none of the patients following Roux GE. Roux gastrojejunostomy during open abdomen exploration in patients with unresectable pancreatic cancer is easy to perform, decreases the incidence of DGE and lowers hospitalization time.

Left Posterior Approach Pancreaticoduodenectomy with Total Mesopancreas Excision and Circumferential Lymphadenectomy Around the Superior Mesenteric Artery for Pancreatic Head Carcinoma

In most cases of pancreatic head cancer, surgery often results in noncurative resection, which is frequently related to inadequate clearance of the mesopancreas. The aim of this report is to introduce the surgical technique of left posterior approach pancreaticoduodenectomy (PD) with total mesopancreas excision and circumferential lymphadenectomy around the superior mesenteric artery (SMA) (LPA-PD) and to examine whether this procedure increases the rate of true curative resection and decreases the rate of locoregional recurrence. Nineteen patients underwent standard PD, and 19 patients underwent LPA-PD. The demographic characteristics, intraoperative outcomes (mean operative time and mean blood loss), postoperative outcomes (complications, type of recurrence and survival), and pathological findings (R number, number of removed regional lymph nodes and positive resection margins) were evaluated. The patient characteristics did not differ significantly between the groups. The mean blood loss in the LPA-PD group was significantly less than that in the standard PD group (p<0.05). The incidence rate of postoperative complications did not differ between the groups. No surgery-related deaths occurred in either group. The number of removed regional lymph nodes around the superior mesenteric artery in the LPA-PD group was significantly greater than that in the standard PD group (p<0.01). The R0 resection rate in the LPA-PD group was higher, although not significantly so, than that in the standard PD group. The resection margin of the mesopancreas was negative in all patients of the LPA-PD group. The rate of locoregional recurrence in the LPA-PD group was significantly lower than that in the standard PD group (p<0.01). The postoperative survival rate did not differ significantly between the groups. Our method of LPA-PD helps secure the negative margin of the mesopancreas and enables complete circumferential lymphadenectomy around the SMA. Therefore, LPA-PD may increase the true curative resection rate and decrease the locoregional recurrence rate compared with standard PD.

Alleviating visceral cancer pain in patients with pancreatic cancer using cryoablation and celiac plexus block

Little is known about the effects of pancreas cryoablation (PCA) on abdominalgia in pancreatic cancer patients or its synergism with celiac plexus block (CPB). In patients without abdominalgia, to investigate the effects of PCA; in patients with abdominalgia, to investigate the pain-alleviating effects of PCA+CPB. Sixty-two patients were enrolled in this retrospective review; 12 without abdominalgia refused PCA, 15 without abdominalgia received PCA to reduce their tumor load and 35 with abdominalgia received PCA+CPB to reduce tumor load and alleviate pain. All PCA and PCA+CPB procedures were performed successfully. Some slight adverse effects (e.g. increased serum amylase, abdominal distension and nausea, abdominal bleeding) had disappeared by 3weeks, spontaneously or after symptomatic treatment. In patients without abdominalgia, pain occurred in one-third of cases (all with pancreatic head cancer) after PCA but had stopped 1–12days after treatment; in patients with abdominalgia before treatment, pain stopped immediately after PCA+CPB in 18 cases and 2–24days after treatment in 17 (all with pancreatic head cancer); a significant difference was found between pretreatment and post-treatment pain frequency (P=0.0019), regardless of the presence of advanced (P=0.0096) or metastatic (P=0.0072) cancer. The average time to pain relief was approximately 7days after both PCA and PCA+CPB, and abdominalgia did not recur for more than 8weeks. PCA may cause short-term pain in some pancreatic cancer patients. Combined PCA+CPB can alleviate cancer pain for more than 8weeks, without severe side effects.

Resection margin involvement and tumour origin in pancreatic head cancer (Br J Surg 2012 99 1036–1049)

Abstract The Editors welcome topical correspondence from readers relating to articles published in the Journal. Responses should be sent electronically via the BJS website (www.bjs.co.uk). All letters will be reviewed and, if approved, appear on the website. A selection of these will be edited and published in the Journal. Letters must be no more than 250 words in length.

Authors' reply: Resection margin involvement and tumour origin in pancreatic head cancer (Br J Surg 2012 99 1036–1049)

Authors' reply: Resection margin involvement and tumour origin in pancreatic head cancer (<i>Br J Surg</i> 2012 99 1036–1049)

Prospective randomized controlled study comparing cell block method and conventional smear method for bile cytology

There is a paucity of data on the cell block (CB) method for bile cytology. We compared the diagnostic efficacy of the CB method with that of conventional smear cytology for bile obtained by endoscopic retrograde cholangiopancreatography (ERCP) in a randomized controlled trial manner. A total of 137 patients with biliary tract lesions suspicious of malignancy who had undergone bile collection under ERCP were recruited to this study. After sampling, the bile was randomized to the CB method (n = 69) or to smear cytology (n = 68). CB sections were prepared using the sodium alginate method and subjected to hematoxylin-eosin, Alcian blue-periodic acid-Schiff stain, and immunohistochemical stains. Both Papanicolaou and Giemsa stains were used for smear cytology. The final diagnosis was malignancy in 94 patients: bile duct cancer, 42; pancreatic head cancer, 34; gallbladder cancer, 16; and ampullary cancer, two. The diagnostic accuracy of the CB method and that of smear cytology were 64% and 53%, respectively (P = 0.20). The sensitivity of the CB method (53%) was significantly better than that of smear cytology (28%; P = 0.014). Their respective sensitivities were 80% and 31% (P = 0.002) for bile duct cancer, 20% and 15% (P = 1.0) for pancreatic head cancer, and 30% and 67% (P = 0.30) for gallbladder cancer. The CB method for bile cytology showed a higher diagnostic yield than smear cytology. Its diagnostic sensitivity was satisfactory in cases of bile duct cancer.

A comparison of the clinical features and prognosis of pancreatic head cancer with that of other periampullary cancers.

Our purpose was to compare the clinical features and prognosis of pancreatic head cancer with that of other periampullary cancers. The medical records of 82 patients (mean age of 61.67±10.52 years) with ductal adenocarcinoma of the head of pancreas and 73 patients (mean age of 60.52±11.72 years) with other periampullary adenocarcinomas, all of whom had received radical surgery, were retrospectively analyzed. There were no significant differences in age and gender between the groups (both, p>0.05). However, there were significant differences in lymph node metastasis, TNM stage, clear surgical margins, tumor size, and neural invasion between the 2 groups (all p<0.05). Patients with pancreatic head adenocarcinoma had significantly higher red blood cell (RBC) count and hemoglobin (Hb), albumin and pre-albumin levels, and higher platelet and white blood cell (WBC) counts than the patients with other periampullary adenocarcinomas (all p<0.05). No differences in carcinoembryonic antigen (CEA) or CA19-9 were noted between the groups. The 1-year survival rates were not different between the groups (p=0.299). Pancreatic head carcinoma has different clinical manifestations and biological features than other periampullary cancers.

Endoneurial Macrophages Induce Perineural Invasion of Pancreatic Cancer Cells by Secretion of GDNF and Activation of RET Tyrosine Kinase Receptor

Perineural invasion of cancer cells (CPNI) is found in most patients with pancreatic adenocarcinomas (PDA), prostate, or head and neck cancers. These patients undergo palliative rather than curative treatment due to dissemination of cancer along nerves, well beyond the extent of any local invasion. Although CPNI is a common source of distant tumor spread and a cause of significant morbidity, its exact mechanism is undefined. Immunohistochemical analysis of specimens excised from patients with PDAs showed a significant increase in the number of endoneurial macrophages (EMΦ) that lie around nerves invaded by cancer compared with normal nerves. Video microscopy and time-lapse analysis revealed that EMΦs are recruited by the tumor cells in response to colony-stimulated factor-1 secreted by invading cancer cells. Conditioned medium (CM) of tumor-activated EMΦs (tEMΦ) induced a 5-fold increase in migration of PDA cells compared with controls. Compared with resting EMΦs, tEMΦs secreted higher levels of glial-derived neurotrophic factor (GDNF), inducing phosphorylation of RET and downstream activation of extracellular signal-regulated kinases (ERK) in PDA cells. Genetic and pharmacologic inhibition of the GDNF receptors GFRA1 and RET abrogated the migratory effect of EMΦ-CM and reduced ERK phosphorylation. In an in vivo CPNI model, CCR2-deficient mice that have reduced macrophage recruitment and activation showed minimal nerve invasion, whereas wild-type mice developed complete sciatic nerve paralysis due to massive CPNI. Taken together, our results identify a paracrine response between EMΦs and PDA cells that orchestrates the formation of cancer nerve invasion.

The surgical resectability following neoadjuvant therapy in pancreatic head cancer

s / Pancreatology 526 Objectives. Alcohol is a risk factor for acute pancreatitis. In our previous two year follow up abstinence protected for recurrences. Our aim was to further determine recurrence of pancreatitis and later pancreatic function in patients who quit drinking after the first episode of alcoholassociated pancreatitis. Materials andmethods: Out of the total of 120 patients with their first alcohol-associated pancreatitis, 23 (20 M, 3 F; age median 47 (27–60) years) met the inclusion criteria for abstinence during the follow up. The criteria for abstinence were alcohol consumption less than 24 grams per twomonths (self-estimated) which is in line with questionnaires detecting alcohol consumption and dependency (Alcohol Use Disorders Identification Test, AUDIT < 8 and Short Alcohol Dependence Data, SADD < 9). Recurrent attacks of acute pancreatitis were studied. Smoking, body-mass index and laboratory tests detecting heavy use of alcohol were recorded. Blood and fecal tests were studied to assess endocrine and exocrine pancreatic function. Results: During a mean follow up time of 4.8 (2–9) years and total of 111 patient years therewere no recurrent attacks of acute pancreatitis. Two patients had diabetes prior to and two just after the first episode of acute pancreatitis. One patient demonstrated new onset diabetes during the follow up at 1.5 years. One patient showed low elastase activity at 2 and another at 3 years, but no-one later on. Conclusions: Abstinence after the first acute alcohol-associated pancreatitis protects from recurrent attacks and seems to decrease the risk for pancreatic dysfunction.

Proton Therapy May Allow Elective Nodal Coverage in the Setting of Neoadjuvant Radiation Therapy for Pancreatic Head Cancers Without Significantly Increasing Normal Tissue Exposure

Neoadjuvant radiation therapy has the potential to improve local disease control and cure rates for patients with localized pancreatic head cancers. Concern about an increased risk of surgical complications due to small bowel and gastric exposure however has limited the enthusiasm for this approach among many surgeons. Dosimetric studies have demonstrated the potential for proton therapy to reduce intestinal exposure compared with x-ray based therapy. The current study attempts to determine if proton therapy may further allow for field expansions to cover high-risk nodal stations in the setting of neoadjuvant radiation therapy.

Bcl-2 associated anthanogen-1 (Bag-1) expression and prognostic value in pancreatic head and periampullary cancer

The expression of anti-apoptosis gene Bcl-2 associated anthanogen-1 (Bag-1), has been associated with outcome in several cancer types, however its prognostic role in pancreatic cancer is unknown. Aim was therefore to evaluate expression of Bag-1 in two anatomically closely related however prognostically different tumours, pancreatic head- and periampullary cancer and correlate expression with outcome.Bag-1 protein expression was studied by immunohistochemistry on original paraffin embedded tissue from 217 patients with microscopic radical resection (R0) of adenocarcinoma of the pancreatic head or periampullary region. Expression was assessed for associations with recurrence free- (RFS), cancer specific- (CSS), overall survival (OS) and conventional prognostic factors.Nuclear Bag-1 was present in 80% of tumours. In 40% Bag-1 resided in the cytosol, which was almost exclusively associated with nuclear expression. Nuclear Bag-1 protein was identified as an independent factor predicting a favourable outcome following radical resection of pancreatic head cancer. Eighteen percent of patients with nuclear Bag-1 were recurrence free and alive 5years following surgery compared to none of the patients lacking expression. In periampullary cancer Bag-1 was not associated with outcome. In conclusion, Bag-1 was present in the majority of both pancreatic head- and periampullary cancers. However it was only identified as a discriminator of outcome in pancreatic head cancer.

Tumour basement membrane laminin expression predicts outcome following curative resection of pancreatic head cancer

Background:Although widely fragmented BMs have been associated with adverse outcome in several cancer types, comparatively little is known with respect to its effect on the prognosis of pancreatic cancer. The aim of the current study was therefore to determine the prognostic value of tumour basement membrane (BM) continuity in two anatomically closely related, however, prognostically different tumours, pancreatic head- and periampullary cancer.Methods:Tumour BM continuity was determined by immunohistochemical staining of its two major components, laminin and collagen type IV. Associations were made with recurrence free survival (RFS), cancer-specific survival (CSS), overall survival (OS) and conventional prognostic factors.Results:Fifty-nine and 61% of pancreatic head and periampullary tumours, respectively, showed limited BM laminin expression. Whereas 43% and 41% of pancreatic head and periampullary cancers, respectively, showed limited BM collagen type IV expression. Limited BM laminin was associated with poor outcome following curative resection of pancreatic head cancer (P=0.034, 0.013 and 0.017 for RFS, CSS and OS, respectively). Two and a half times as many patients with ⩾25% BM laminin were recurrence free and alive 5 years following resection compared with those with limited BM laminin. Although staining patterns of both BM components were weakly correlated with each other, BM collagen type IV expression was not significantly associated with outcome in either tumour type.Conclusion:Discontinuous BMs, determined by laminin expression, are associated with poor outcome following curative resection of pancreatic head cancer.

Distribution of metastatic lymph nodes in 150 patients who underwent radical resection for pancreatic head cancer

Objective To study the characteristics and the impact of lymph node metastasis on radical resection for pancreatic head cancer to provide a theoretical basis for lymphadenectomy in radical resection.To study the reliability of using a surgical microscope to detect lymph nodes in radically resected specimens of pancreatic head cancer.Methods Lymph nodes in the specimens after radical pancreaticoduodeneetomy (pancreaticoduodenectomy + D2 regional lymphadenectomy) were identified using a surgical microscope and they were grouped using the JPS standard.The position and the frequency of the lymph nodes retrieved,and their association with other clinicopathologic factors were analysed.The results were compared with the data published in 2004 on 46 patients to evaluate the reliability of using a surgical microscope.Results Lymph node metastasis was detected histopathologically in 101 patients (67.3％).The median number of lymph nodes retrieved in the specimens as detected using the surgical microscope was 38.2.The most commonly involved lymph node groups were No.13 (64.5％),No.14 (51.7％),No.17 (38.6％),No.12 (25.8％),No.16 (20.8％).Lymph node metastasis was significantly associated with tumour T stage,tumour invasion and differentiation,preoperative serum level of CA19-9 and CA72-4,but not with patient age,sex,or tumour location.There were no significant differences between the results and the data of the previous study in 2004.Conclusions Extended lymphadenectomy is necessary because extensive lymph node metastasis was common.Surgical microscopy is an effective and reliable method to detect lymph nodes in resected specimens of pancreatic head cancer for accurate pathologic staging. Key words: Pancreatic neoplasms; Pancreaticoduodenectomy; Lymphatic metastasis; Surgical microscope