A Prospective, Single-Arm, Single-Center, Case Series to Determine the Feasibility of Safe Skill Transfer for Transabdominal Preperitoneal (TAPP) Repair Utilizing a Hands-On Mentorship Model.

OBJECTIVES: It is difficult to introduce laparoscopic surgery in institutions with a small number of patients, and surgical training relies heavily on mentors to produce well-trained surgeons. The aim of this study was to determine whether implementation of a hands-on mentorship model could provide safe skill transfer for transabdominal preperitoneal (TAPP) repair. METHODS: A trainee who had no experience with TAPP repair underwent operative tutorials until the mentor judged that the trainee could carry out the operation independently. Ten patients who underwent an elective TAPP repair were prospectively enrolled in this study. RESULTS: No cases had over 5 mL of bleeding, intraoperative/postoperative complications, or recurrence. There were significant differences in operation times between the first 4 cases and the later 5 cases, except for a bilateral inguinal hernia case. CONCLUSION: A prospective, single-arm, single-center, case series showed the feasibility of safe skill transfer for TAPP repair using a hands-on mentorship model.

The first case of huge amebic intra-abdominal tumor with asymptomatic amebic colitis.

We report a rare case of huge amebic intra-abdominal tumor with asymptomatic amebic colitis. This appears to represent the first report of amebic intra-abdominal tumor. A 31-year-old woman presented to a local doctor with only a sensation of abdominal fullness. Abdominal computed tomography (CT) showed a huge intra-abdominal tumor in the left abdominal cavity, and she was referred to our hospital. Colonofiberscopy for detailed examination showed multiple slight, discrete ulcers in the cecum. Ameboid trophozoites were identified from biopsy specimens, and asymptomatic amebic colitis was diagnosed. Oral metronidazole (MTZ) was administered at 1500 mg/day for 10 days. CT 14 days after starting MTZ showed no change in the intra-abdominal tumor, and resection of the tumor was therefore performed. Pathological examination revealed Entamoeba histolytica with engulfed erythrocytes complicated by hemorrhagic cyst. If an intra-abdominal tumor is present and colitis is observed, amebic intra-abdominal tumor should be considered among the differential diagnoses.

A case study of a collision tumor composed of cancers of the bile duct and pancreas.

In this case report, we describe the extremely rare case of a collision tumor comprising cancers of the bile duct and the pancreas. A 70-year-old man was referred to our hospital with a diagnosis of obstructive jaundice. He was diagnosed with pancreatic head cancer, and we performed a pancreaticoduodenectomy with lymph node dissection. At laparotomy, there were two palpable masses in the vicinity of the confluence of the cystic duct and the head of the pancreas. The resected specimen demonstrated tumors at the confluence of the cystic duct and in the pancreatic head. Histopathological examination demonstrated a moderately differentiated tubular adenocarcinoma in the pancreatic head and a well-differentiated tubular adenocarcinoma at the confluence of the cystic duct. Immunostaining was negative for p53 and MUC6 in the pancreatic head tumor; however, immunostaining was positive for both in the tumor located at the confluence of the cystic duct. The two tumors were histologically different and were diagnosed as collision cancer caused by the collision of the bile duct and pancreatic cancers.

Clinical significance of wall invasion pattern of subserosa-invasive gallbladder carcinoma.

We have previously classified wall invasion patterns of gallbladder carcinoma (GBC) cases into two groups, i.e., the infiltrative growth type (IG type) and destructive growth type (DG type). The DG type was significantly associated with poor differentiation, aggressive infiltration and decreased postoperative survival in terms of its histological differentiation, lymphatic invasion, venous invasion, lymph node status, neural invasion and mode of subserosal infiltration. In the present study, we analyzed 42 surgically-resected subserosal invasive gallbladder adenocarcinomas, invading the perimuscular connective tissue (pT2). The cumulative 5-year survival rate in the series was 48.7%. Lymphatic invasion (p=0.021), venous invasion (p=0.020), mode of subserosal infiltration (p<0.001), histological differentiation (p=0.030) and biliary infiltration (p=0.007) were noted, respectively, at a significantly higher incidence in more aggressive infiltration or poor differentiation in the DG type. The cumulative 5-year survival rate of curative resection cases was lower in patients with the DG type than in those with the IG type (68.9 versus 20.2%, respectively, p=0.006, log-rank test). On Cox's proportional hazard regression modeling, the low degree of venous/perineural invasion and IG type of wall invasion pattern were associated with a significant improvement in overall survival. Our data suggest that the wall invasion pattern is an independent predictor of survival in subserosal invasive GBC. Regarding the clinical application of our concept, on the classification of patients with subserosal invasive GBC based on a combination of the wall invasion pattern and lymph node status, the overall survival rate in patients with the DG type and/or N2 metastasis (n=21) was lower than in patients with the IG type and N0, 1 metastasis (n=21) (p=0.0023, log-rank test). The wall invasion pattern could contribute to decision-making concerning curative resection for subserosal invasive GBC.

Multicenter study of serous cystic neoplasm of the Japan pancreas society.

OBJECTIVES: There have been only a few reports on follow-up results of serous cystic neoplasm (SCN) of the pancreas. The frequency of malignancy and surgical indication of SCN are not determined yet. METHODS: In this multi-institutional study of the Japan Pancreas Society, a total of 172 patients with SCN were enrolled. The mean follow-up period was 4.5 years. Surgical resection was performed in 90 patients, whereas the remaining 82 were simply observed. RESULTS: Of all patients, 20% were symptomatic. The tumor was located in the pancreatic head (39%), body (35%), and tail (22%). The mean diameter of the tumor was 4.1 cm. None of the patients showed distant or lymph node metastasis except for liver metastasis found in 2 patients (1.2%). No patient died during the follow-up. The preoperative diagnosis did not correctly identify SCN in 57 (63%) of 90 resected cases. A honeycomb appearance, which is one of the most characteristic findings of SCN, could be diagnosed better by endoscopic ultrasonography than by other imaging diagnostic modalities. CONCLUSIONS: Surgical resection should be considered only when clear distinction from other surgical diseases is difficult, when symptoms or mass effects are present, and when the tumor size is large.

An annular pancreas associated with carcinoma of the papilla of Vater: report of a case.

An annular pancreas is an uncommon congenital anomaly that usually presents early in childhood. Malignancy in the setting of an annular pancreas is unusual. We herein report a case of annular pancreas with carcinoma of the papilla of Vater. A 59-year-old man presented with epigastric discomfort and was referred to us after gastroduodenal endoscopy showed a tumor of the papilla of Vater. Preoperative imaging showed the pancreatic parenchyma encircling the descending duodenum and a tumor at the papilla of Vater. A pancreaticoduodenectomy was performed for the annular pancreas and the ampullary tumor. Histological examination confirmed a complete annular pancreas and carcinoma in situ of the papilla of Vater. We also provide a review of the reported cases of an annular pancreas with periampullary neoplasms and discuss the clinical characteristics of this anomaly.

Complete response after short-term sorafenib treatment in a patient with lymph node metastasis of hepatocellular carcinoma.

A 60-year-old man received interferon/ribavirin combination therapy for chronic hepatitis C in 2002 and achieved sustained virological response. In 2008, a hepatocellular carcinoma (HCC) with a diameter of 60 mm appeared and surgical resection was performed. In March 2011, the patient was referred to our hospital because of portal lymph node swelling. Abdominal ultrasonography, dynamic CT and dynamic MRI did not show any tumors in the liver, but revealed portal lymph node swelling (18 × 11 mm). Taking the elevation of serum des-γ-carboxy prothrombin and alpha-fetoprotein levels, including the lectin-bound type, into consideration, we made the diagnosis of HCC metastasis to the portal lymph node. We started sorafenib therapy at a dose of 800 mg/day, but discontinued it after 11 days due to grade 3 hand-foot skin reaction and rash. In spite of treatment termination, portal lymph node swelling disappeared and the serum des-γ-carboxy prothrombin and alpha-fetoprotein levels normalized. We considered that our patient achieved complete response to sorafenib according to the Response Evaluation Criteria in Solid Tumors (RECIST). The patient maintains remission up to June 2012, more than 1 year after the discontinuation of sorafenib therapy. Sorafenib could be a good option for unresectable or recurrent HCC.

Leiomyosarcoma of the pancreas: report of a case.

Leiomyosarcoma of the pancreas is a rare neoplasm, with only 34 reported cases in the literature. We encountered a rare case of leiomyosarcoma of the pancreas, treated successfully by surgery. A 41-year-old woman was referred to our hospital for further examinations of a pancreatic tumor. Imaging studies demonstrated a solid and lobular mass, about 4 cm in diameter, in the body of pancreas. This mass had a nonuniform content and was encapsulated. We performed distal pancreatectomy and splenectomy for an assumed diagnosis of invasive ductal carcinoma. Macroscopically, a sagittal section of the operative specimen showed a well-circumscribed yellowish-white mass without any cystic changes. Immunohistological examination revealed that α-smooth muscle actin, desmin, and vimentin were positive, and the labeling index of MIB-1 was 50% or more. Based on these findings, we confirmed a diagnosis of leiomyosarcoma originating from the pancreas. During 14 months of follow-up to date, there has not been any evidence of local recurrence or distant metastasis.

Nonfunctioning pancreatic endocrine tumor with extension into the main pancreatic duct: report of a case.

Pancreatic endocrine tumors (PETs) rarely involve the main pancreatic duct. We report a case of malignant nonfunctioning pancreatic endocrine tumor (NFPET) with prevalent intraductal growth. A 47-year-old woman was referred to us after ultrasonography at a routine health check showed diffuse swelling of the pancreas. Preoperative imaging showed a solid mass in the tail of the pancreas and a bulging intraductal mass in the main pancreatic duct. We performed total pancreatectomy because the tumor occupied almost the entire lumen of the main pancreatic duct. Histological examination confirmed well-differentiated endocrine carcinoma. We review reported cases of the intraductal growth of NFPETs and discuss the pathogenesis of these unusual tumors.

Natural history of branch duct intraductal papillary mucinous neoplasms of the pancreas: a multicenter study in Japan.

OBJECTIVE: The aim of this study was to evaluate the long-term follow-up results of patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) without mural nodules (MNs) at 10 representative institutions in Japan. METHODS: We analyzed 349 follow-up BD-IPMN patients who had no MNs on endoscopic ultrasonography at initial diagnosis. RESULTS: Observation periods ranged from 1 to 16.3 years (median, 3.7 years). Sixty-two (17.8%) patients exhibited disease progression during follow-up. Twenty-two underwent surgery, leading to a pathological diagnosis of carcinoma in 9 and adenoma in 13. Although the remaining 287 (82.2%) showed no changes, 7 underwent surgery because of symptoms (n = 2), choice (n = 2), or development of pancreatic ductal adenocarcinoma (n = 3); all of them were diagnosed pathologically as adenomas. Of the 29 patients undergoing surgery, all 9 with carcinoma exhibited signs of progression, such as increased main pancreatic duct diameter and/or appearance of MNs. Pancreatic ductal adenocarcinomas and additional BD-IPMNs developed in 7 (2.0%) and 13 (3.7%), respectively. Overall, 320 (91.7%) patients were followed without surgery. CONCLUSIONS: Most BD-IPMN patients who had no MNs on endoscopic ultrasonography could be managed without surgery. However, careful attention should be paid to disease progression and the development of pancreatic ductal adenocarcinomas during follow-up.

Clinicopathological features and prognosis of mucinous cystic neoplasm with ovarian-type stroma: a multi-institutional study of the Japan pancreas society.

OBJECTIVE: The aim of this study was to elucidate the clinicopathological features and prognosis of mucinous cystic neoplasms (MCNs). MATERIALS AND METHODS: We performed a multi-institutional, retrospective study on a collected series of patients with MCN pathologically defined by ovarian-type stroma. Clinicopathological features and prognosis were investigated. RESULT: Mucinous cystic neoplasm was confirmed in 156 cases, including 129 adenomas (82.7%) and 21 noninvasive (13.4%) and 6 invasive carcinomas (3.9%). Patients with MCN were exclusively women (98.1%) with the mean age of 48.1 years. All but 1 MCN were in the pancreatic body/tail region with a mean size of 65.3 mm. Communication between the cyst and the pancreatic duct was found in 18.1%. The 3-, 5-, and 10-year survival rates were 97.6%, 96.6%, and 96.6%, respectively. A significant difference in the survival rates was observed between adenomas and carcinomas and between minimally invasive carcinomas and invasive carcinomas. Cyst diameter and presence of mural nodule were predictive of malignant MCN. CONCLUSIONS: Mucinous cystic neoplasm is a rare but distinctive pancreatic cystic neoplasm with a favorable overall prognosis. All MCNs should be resected to prevent malignant changes but can be observed for an appropriate time when the lesion is small without the presence of mural nodules.

[Retroperitoneal liposarcoma: a case report].

A 35-year-old woman who had visited an other hospital because of epigastralgia and anorexia was found to have a giant abdominal tumor, and was referred to our hospital. On admission, the abdomen was markedly distended. Abdominal CT scan and MRI showed the presence of a retroperitoneal tumor which occupied almost the entire abdominal cavity. She was operated a under a diagnosis of retroperitoneal liposarcoma. The tumor was located between the subphrenic space and the pelvic cavity, and was compressing the stomach, duodenum, pancreas and colon. Removal of the retroperitoneal tumor, including the right kidney, was performed. The resected tumor was 34 × 28 × 20 cm, weighed 5.5 kg and showed a variety of finding. The pathological diagnosis was a mixed type of retroperitoneal liposarcoma, consisting of well-differentiated type and myxoid type. We reported a case of giant retroperitoneal liposarcoma, with a review of the literature.

The distance of tumor spread in the main pancreatic duct of an intraductal papillary-mucinous neoplasm: where to resect and how to predict it.

BACKGROUND: The surgical decision regarding where to resect the pancreas is an important judgement that is directly linked to the surgical procedure. An appropriate surgical margin to resect intraductal papillary-mucinous neoplasm (IPMN) of the pancreas based on the distance of tumor spread (DTS) in the main pancreatic duct has not been adequately documented. We analyzed the appropriate surgical margin based on the DTS in the main pancreatic duct of IPMN and the positive rate at the pancreatic cut end margin. METHODS: Forty patients with main duct- or mixed-type IPMN diagnosed histopathologically who underwent surgery at Tokai University Hospital between 1991 and 2008 were retrospectively analyzed. The resection line was determined to achieve a 2-cm surgical margin in patients with main duct- or mixed-type IPMN and as limited a resection as possible to remove the dilated branch duct in patients with branch duct-type IPMN according to macroscopic type. The dysplastic state of the epithelium was judged as positive for carcinoma in situ (high-grade dysplasia) or adenoma (very low to moderate dysplasia) and judged as negative for hyperplasia or normal. RESULTS: The mean DTS in the main pancreatic duct was 41.6 +/- 30.0 mm, and that of the distance of tumor absence was 13.6 +/- 12.4 mm. The positive rate at the pancreatic cut end margin in frozen sections was 29.7%. The final positive rate at the pancreatic cut end margin was 26.2%. There has been no evidence of local recurrence in the remnant pancreas. DTS in the main pancreatic duct of IPMN was correlated with the maximum diameter of the duct (R = 0.678). CONCLUSION: Distance of tumor spread offered important insights about the appropriate site to resect the pancreas and the positive rate at the cut end margin in IPMN.

Stromal thrombospondin-1 expression is a prognostic indicator and a new marker of invasiveness in intraductal papillary-mucinous neoplasm of the pancreas.

The invasion of intraductal papillary-mucinous neoplasm (IPMN) is sometimes difficult to diagnose using only ordinary hematoxylin-eosin sections. The aim of this study was to evaluate the invasion of IPMN more precisely using thrombospondin-1 (TSP1) immunohistochemistry as a useful adjunct to morphological examination. Eighty patients that underwent primary resection for pancreatic IPMNs were retrospectively analyzed. The 80 IPMNs were studied for the expression of TSP1, MUC1-CORE, MUC2, and MUC5AC. The cases were evaluated for dysplasia, the presence of invasion, hisological subtypes, and survival. The 80 IPMNs were classified into 29 intraductal papillary-mucinous adenomas (IPMAs), 10 borderline IPMNs, 18 noninvasive intraductal papillary-mucinous carcinomas (IPMCs), and 23 invasive IPMCs according to the WHO classification. Invasive IPMCs were further divided into 12 minimally invasive IPMCs (MI-IPMCs) and 11 invasive carcinomas originating from IPMCs (IC-IPMCs) according to the Japan Pancreatic Society classification. The rate of strongly positive cases with more than 30% of the cancer stroma area expressing TSP1 was significantly higher in MI-IPMC and IC-IPMC than in noninvasive IPMC (P = 0.035, 0.005). Furthermore, patients in the strongly positive group had a significantly poorer prognosis compared to patients in the negative-weakly positive group (P = 0.008, log-rank test). Of the 80 tumors, 22 were classified into gastric-, 45 into intestinal-, 7 into pancreatobiliary-, and 6 into oncocytic-type IPMNs according to criteria described previously. The cases with a strongly positive expression of TSP1 were frequently detected in the pancreatobiliary and oncocytic types (P = 0.001). In conclusion, stromal TSP1 expression is a prognostic indicator and a new marker of invasiveness in IPMN.

First case of primary phyllodes tumor of the pancreas: case report and findings of immunohistochemical and ultrastructural studies.

A 37-year-old Japanese man with a solid and cystic pancreatic mass was referred to our hospital. Computed tomography revealed a well-demarcated solid and cystic mass measuring approximately 3.0 cm in diameter in the pancreatic body. The patient underwent middle segment pancreatectomy, and the retrieved tumor specimen was found to be a well-demarcated solid and cystic lesion measuring 3.0 x 3.0 cm. On histological examination, the cyst walls were found to be lined with a monolayer of non-atypical tall columnar epithelial cells. The solid areas surrounded the cystic ones and showed storiform proliferation of spindle cells that contained round, oval, or elongated nuclei and were present among abundant collagen fibers. The solid areas sent phylloid projections into the cystic spaces and the main pancreatic duct. The spindle cells were found to be diffusely positive for alpha-smooth muscle actin, desmin, and h-caldesmon on immunohistochemical analysis. Electron microscopy revealed that these cells possessed well-developed myofilaments with dense bodies, pinocytic vesicles, and basal lumina. Neither metastasis nor local invasion was detected. After the operation (4 years), tumor recurrence has not occurred. The main differential diagnoses of spindle cell tumors are leiomyomas, leiomyosarcomas, inflammatory myofibroblastic tumors, solitary fibrous tumors, extra-gastrointestinal stromal tumors, and schwannomas. However, the histological findings in the present case differed from those of these tumors. The present lesion is the first reported case of a primary pancreatic phyllodes tumor.

Wall-invasion pattern correlates with survival of patients with gallbladder adenocarcinoma.

Gallbladder carcinomas (GBC) frequently show vascular invasion and metastasis when the carcinoma cells invade the perimuscular connective tissue (pT2 according to the TNM classification) through the muscular layer. In this study, two intramural invasion patterns were defined as (i) infiltrative growth (IG) type, infiltrative growth in the muscle layer without destruction and (ii) destructive growth (DG) type, massive growth with destruction of the muscle layer. Sixty-six surgically resected gallbladder adenocarcinomas invading the perimuscular connective tissue (pT2) and beyond the gallbladder wall, including the visceral serosa, (pT3/pT4) were examined. The overall survival rate of the patients with the DG type was significantly lower than that of the patients with the IG type (p = 0.018). Lymphatic invasion (37.5% of IG and 62.5% of DG, p = 0.014), venous invasion (41.9%, 58.1%, p = 0.089), nodal status (30.4%, 69.6%, p = 0.015) and scirrhous growth (INFgamma) (31.0%, 69.0%, p = 0.0035) were more frequently detected in DG cases than in IG cases. In addition, median survival and survival rates were statistically analyzed. The patients with a high grade of lymphatic and venous invasion had lower survival rates (p < 0.0001 and p < 0.05, respectively). The patients with the DG type and scirrhous growth (INFgamma) also had lower survival rates (p < 0.05 and p < 0.0001, respectively) than did patients with the IG type and expansive/intermediate growth (INFalpha,beta). On multivariate analysis, neural invasion (odds ratio, 0.157; 95% confidence interval, 0.039-0.629) was an independent predictor of mortality. In conclusion, the DG invasion pattern is an indicator of high malignant potential and indirectly worsens the prognosis of patients with gallbladder adenocarcinoma.

Stromal laminin-5gamma2 chain expression is associated with the wall-invasion pattern of gallbladder adenocarcinoma.

Our previous study demonstrated that the pT2 and pT3-4 gallbladder carcinomas can be classified into two groups, i.e. infiltrative growth type (IG type) and destructive growth type (DG type) and that the DG type is associated with poor differentiation, aggressive infiltration, and decreased postoperative survival. The present study focused on the clinicopathologic significance of laminin-5gamma2 chain expression as an indicator of local aggressiveness and Ki-67 labeling index (Ki-67 LI) as an indicator of the cell proliferation activity of gallbladder carcinoma. Ki-67 LI was higher in the DG type (26.3%) than in the IG type (21.4%), and the rate of high-grade cell proliferation cases (Ki-67 LI > or = 30%) was high in the DG type (P = 0.012). Gallbladder carcinoma cases with high Ki-67 LI were significantly associated with poorly differentiation (P = 0.089) and distant lymph node metastasis (P = 0.079). Laminin-5gamma2 expression patterns of gallbladder carcinoma were divided into two distinct types, extracellular staining and cytoplasmic staining. The extracellular staining was subclassified into two groups, basement membrane staining and stromal staining. In the basement membrane staining, laminin-5gamma2 was present in the basement membranes surrounding neoplastic glandular structures. The basement membrane staining of laminin-5gamma2 was more frequent in the IG type (40%) than in the DG type (12.9%) (P = 0.025). The stromal staining was more frequent in the DG type. Furthermore, the stroma-positive group was more closely associated with decreased overall survival than the stroma-negative group (P = 0.028). The cytoplasmic staining was not significantly correlated with invasion pattern in gallbladder carcinoma (P = 0.545). Univariate analysis demonstrated that laminin-5gamma2 stromal staining is a predictor of lymphatic invasion, venous invasion, neural invasion, the mode of subserosal infiltration, and lymph nodal status. Multivariate analysis revealed the mode of subserosal infiltration is the strongest predictor of stromal invasion (P = 0.068). In conclusion, high-grade cell proliferation and stromal laminin-5gamma2 staining were significantly correlated with a wall-invasion pattern of aggressive gallbladder carcinoma indicating destructive growth (DG type).

Curative surgical treatment after preoperative chemotherapy for primarily inoperable locally advanced pancreatic carcinoma: report of a case.

Pancreatic cancer is considered resectable only when there are no distant metastases or infiltration of surrounding organs or arteries. We describe a patient with primarily inoperable locally advanced pancreatic adenocarcinoma who underwent curative surgical treatment after preoperative chemotherapy. A 61-year-old woman was admitted for further evaluation of a pancreatic head mass discovered fortuitously on a health screening. Examination revealed locally advanced pancreatic cancer with infiltration of the superior mesenteric artery. After a partial response was obtained by chemotherapy with gemcitabine (GEM) and S-1, we performed pancreaticoduodenectomy. Microscopically, the main tumor was replaced with fibrotic tissue, and there were only a few residual adenocarcinoma cells in the pancreatic head. The radicality of the surgery was R0, according to the TNM classification. Our results suggest that neoadjuvant treatment with GEM/S-1 on a sustainable regimen offers the possibility of a multimodal treatment concept for all patients and a higher radical-resection rate in patients with otherwise unresectable pancreatic cancers.