Extent of regional lymphadenectomy and number-based nodal classification for non-ampullary duodenal adenocarcinoma.

BACKGROUND: This study aimed to evaluate the adequate extent of regional lymphadenectomy according to tumor location and the impact of number-based nodal classification on survival in patients with non-ampullary duodenal adenocarcinoma (NADAC). METHODS: A total of 85 patients with NADAC who underwent surgery were enrolled. The frequency of metastasis was calculated for each node group in the respective tumor locations for 63 patients who underwent lymphadenectomy for pT2-pT4 tumor. RESULTS: The frequency of metastasis in the pancreaticoduodenal (nos. 13 and 17) and superior mesenteric artery (no. 14) nodes was high (16.7 %-52.3 %) regardless of tumor location. Metastasis in the perigastric (nos. 3 and 4d) and right celiac artery (no. 9) nodes was not uncommon (14.3 %-22.2 %) for tumors in the first portion. The frequency of metastasis in the pyloric (nos. 5 and 6) and the other peripancreaticoduodenal (nos. 8 and 12) nodes varied depending on tumor location but could not be ignored for staging. When these nodes were classified as regional nodes, the 5-year survival in patients with pN0, pN1 (1-2 positive nodes), and pN2 (≥3 positive nodes) were 82.9 %, 51.7 %, and 19.2 %, respectively (p < 0.001). pN classification independently predicted survival (pN1, p = 0.022; pN2, p < 0.001). CONCLUSIONS: Nos. 5, 6, 8, 12, 13, 14, and 17 nodes in all advanced NADAC and nos. 3, 4d, and 9 nodes in advanced NADAC in the first portion should be considered as regional nodes for accurate staging. The number-based nodal classification allows good patients' prognostic stratification.

Mirizzi Syndrome Type IV Successfully Treated with Peroral Single-operator Cholangioscopy-guided Electrohydraulic Lithotripsy: A Case Report with Literature Review.

A 76-year-old man presented with liver dysfunction and intrahepatic bile duct dilatation. Imaging studies showed two large stones that had become impacted in the common hepatic duct, which was fused with the gallbladder. The patient was diagnosed with Mirizzi syndrome type IV. Hepaticojejunostomy and stone removal failed due to dense gallbladder adhesions involving the right hepatic artery. The bile flow was temporarily restored; however, the patient experienced cholangitis 16 months later. The stones were extracted via peroral single-operator cholangioscopy (SOC)-guided electrohydraulic lithotripsy. This is the first case in which stones were completely removed by SOC-guided treatment in a patient with Mirizzi syndrome type IV.

Long-term outcomes of surgical resection for T1b gallbladder cancer: an institutional evaluation.

BACKGROUND: There is no comprehensive agreement concerning the overall performance of radical resection for T1b gallbladder cancer (GBC). This research focused on addressing whether T1b GBC may spread loco-regionally and whether radical resection is necessary. METHODS: A retrospective analysis was conducted of 1032 patients with GBC who underwent surgical resection at our centre and its affiliated institutions between January 1982 and December 2018. A total of 47 patients with T1b GBC, 29 (62%) of whom underwent simple cholecystectomy and 18 (38%) of whom underwent radical resection with regional lymph node dissection, were enrolled in the study. RESULTS: GBC was diagnosed pre-operatively in 16 patients (34%), whereas 31 patients (66%) had incidental GBC. There was no blood venous or perineural invasion in any patient on histology evaluation, except for lymphatic vessel invasion in a single patient. There were no metastases in any analysed lymph nodes. The open surgical approach was more prevalent among the 18 patients who underwent radical resection (open in all 18 patients) than among the 29 patients who underwent simple cholecystectomy (open in 21; laparoscopic in 8) (P = 0.017). The cumulative 10- and 20-year overall survival rates were 65 and 25%, respectively. The outcome following simple cholecystectomy (10-year overall survival rate of 66%) was akin to that following radical resection (64%, P = 0.618). The cumulative 10- and 20-year disease-specific survival rates were 93 and 93%, respectively. The outcome following simple cholecystectomy (10-year disease-specific survival rate of 100%) was equivalent to that following radical resection (that of 86%, P = 0.151). While age (> 70 years, hazard ratio 5.285, P = 0.003) and gender (female, hazard ratio 0.272, P = 0.007) had a strong effect on patient overall survival, surgical procedure (simple cholecystectomy vs. radical resection) and surgical approach (open vs. laparoscopic) did not. CONCLUSIONS: Most T1b GBCs represent local disease. As pre-operative diagnosis, including tumour penetration of T1b GBC, is difficult, the decision of radical resection is justified. Additional radical resection is not required following simple cholecystectomy provided that the penetration depth is restricted towards the muscular layer and that surgical margins are uninvolved.

Relevance of Dissection of the Posterior Superior Pancreaticoduodenal Lymph Nodes in Gallbladder Carcinoma.

BACKGROUND: This study was designed to evaluate the prognostic value of positive posterior superior pancreaticoduodenal lymph nodes to clarify the need for dissection of these nodes. METHODS: A total of 148 patients with gallbladder carcinoma who underwent radical resection including dissection of the posterior superior pancreaticoduodenal nodes were enrolled. The incidence of metastasis and the survival rates among patients with metastasis to each lymph node group were calculated. RESULTS: Of the 148 patients, 70 (47%) had nodal disease. The incidences of metastasis in the cystic duct, pericholedochal, retroportal, and hepatic artery node groups, defined as regional nodes in the UICC TNM staging system, ranged from 8.3 to 24.3% with 5-year survival rates of 12.5-46.4% in patients with positive nodes. The incidence of metastasis to the posterior superior pancreaticoduodenal nodes was 12.8% with a 5-year survival rate of 31.6% in patients with positive nodes. Survival after resection was significantly better in patients with distant nodal disease affecting only the posterior superior pancreaticoduodenal nodes (5-year survival, 55.6%) than in patients with distant nodal disease beyond these nodes (5-year survival, 15.0%; p = 0.046), whereas survival after resection was comparable between the former group and patients with regional nodal disease alone (5-year survival, 40.7%; p = 0.426). CONCLUSIONS: In gallbladder carcinoma, involvement of the posterior superior pancreaticoduodenal nodes is similar to that of regional nodes in terms of both the incidence of metastasis and the impact on survival. Inclusion of the posterior superior pancreaticoduodenal nodes among the regional nodes should be considered.

[A Case of Hepatocellular Carcinoma with Lymph Node Metastasis Successfully Treated by Multidisciplinary Treatment].

Lymph node metastasis has a poor prognosis in patients with hepatocellular carcinoma(HCC). We report a case of HCC with lymph node metastasis successfully treated by multidisciplinary treatment. An 81-year-old woman who was followed up for liver cirrhosis received a diagnosis of HCC, which was detected by CT as a solitary tumor 20mm in diameter in the couinaud segment 7 of the liver. She underwent transcatheter arterial chemoembolization(TACE)twice for HCC because of her advanced age and no intention to undergo hepatectomy. Some 12 months later, local recurrence was managed by repeat TACE and paraaortic lymph node metastasis by surgical resection. The patient received radiotherapy for mediastinal nodal disease 6 months after the resection. She remains alive and well without no evidence of disease 84 months after the initial treatment. This case and a review of the literature suggest that multidisciplinary treatment with TACE, surgical resection and radiotherapy may provide a survival benefit for selected patients with HCC with isolated lymph node metastasis.

[Resection for a Locally Advanced Duodenal Adenocarcinoma with Obstructive Jaundice and Hepatic and Pancreatic Invasion - A Case Report].

A 64-year-old woman diagnosed with duodenal adenocarcinoma with duodenal stenosis and obstructive jaundice was referred to our hospital. Computed tomography revealed a tumor measuring 9×6 cm in the second portion of the duodenum that had invaded the liver(S6)and head of the pancreas. After percutaneous transhepatic biliary drainage for obstructive jaundice, the patient underwent subtotal stomach-preserving pancreaticoduodenectomy, partial resection of the liver(S6), and partial resection of the colon. Histologic examination showed the primary tumor to be moderately and poorly differentiated adenocarcinoma with hepatic and pancreatic invasion; lymph node metastasis was not found. The patient received S-1 for 1 year and remains alive and well with no evidence of disease 15 months after resection.

[Lymph Node Recurrence of Small Cell Carcinoma of the Extrahepatic Bile Ducts Effectively Treated with Cisplatin plus Irinotecan Chemotherapy - Report of a Case].

A 78-year-old man with jaundice was diagnosed with perihilar cholangiocarcinoma(Bismuth type I ). After endoscopic biliary drainage for jaundice, a subtotal stomach-preserving pancreaticoduodenectomy was performed. Histologic examination and immunohistochemical staining with chromogranin A, synaptophysin, and CD56 resulted in a diagnosis of small cell carcinoma. Of the 18 dissected lymph nodes, 8 nodes contained a metastatic tumor. Left supraclavicular and paraaortic lymph node metastases were detected by computed tomography 5 months after the resection. He received cisplatin plus irinotecan chemotherapy, and after 2 courses of the chemotherapy, both metastatic lesions were reduced in size. He remains alive and well with no evidence of progressive disease after 6 courses of chemotherapy.

[Surgical Resection for Carcinoma Arising from the Remnant Intrapancreatic Bile Duct after Excision of a Congenital Choledochal Cyst - A Case Report].

A 77-year-old woman presented with a high fever. She had a history of resection of the extrahepatic bile duct, cholecystectomy, and hepaticojejunostomy for a congenital choledochal cyst, 23 years previously. Computed tomography showed a tumor measuring 90mm behind the head of the pancreas. This tumor appeared to invade the duodenum and pancreas, although swollen lymph nodes and distant metastasis were not detected. The patient was diagnosed with a carcinoma arising from the intrapancreatic remnant bile duct. A subtotal stomach-preserving pancreaticoduodenectomy and regional lymphadenectomy were performed. The patient remains alive and well with no evidence of disease 11 months after resection.

[Long-Term Survival after Reoperation for Lung Metastasis of Resected Pancreatic Adenocarcinoma - A Case Report].

A 66-year-old woman with pancreatic cancer underwent resection of the pancreatic body and tail. Thirty-seven months after the initial surgery, a tumor was found in S4 of the right lung, for which resection of the middle lobe of the lung was performed. A diagnosis of lung metastasis originating from pancreatic cancer was confirmed based on histological and immunohistopathological assessments. Sixty-seven months after the initial surgery, despite the gemcitabine-based adjuvant chemotherapy, a tumor was detected in S3 of the left lung, for which partial lung resection was performed. Similar to the previous diagnosis, the tumor was diagnosed as lung metastasis of pancreatic cancer on the basis of the pathological findings. After the third operation, despite gemcitabine and S-1 chemotherapy, widespread pulmonary metastasis developed. One hundred and thirty months after the initial surgery, the patient died of respiratory failure due to carcinomatous pleurisy.

Comparison of Number Versus Ratio of Positive Lymph Nodes in the Assessment of Lymph Node Status in Extrahepatic Cholangiocarcinoma.

BACKGROUND: This study aimed to compare the utility of the number of positive lymph nodes with the lymph node ratio (LNR) in predicting survival after resection of extrahepatic cholangiocarcinoma. METHODS: A retrospective analysis of 142 consecutive patients who underwent radical resection of extrahepatic cholangiocarcinoma was performed. A total of 3066 regional lymph nodes were resected. The median number of nodes per patient was 21. The optimal cutoff values for the number of positive nodes and the LNR were determined using the Chi square scores calculated by the Cox proportional hazards regression model. RESULTS: Nodal disease was found in 59 patients (42 %). In the subsequent analysis of the impact that nodal status has on survival, 18 patients with R1/2 resection and 6 patients with paraaortic nodal disease who did not survive for more than 5 years after resection were excluded. The optimal cutoff value for the number of positive nodes was 1, and the optimal cutoff value for the LNR was 5 %. Univariate analysis identified both the number of positive nodes (0, 1, or ≥2; P = 0.005) and the LNR (0, 0-5, or >5 %; P = 0.007) as significant prognostic factors. Multivariate analysis identified the number of positive nodes but not the LNR as an independent prognostic factor (P = 0.012). The 5-year survival rates were 64 % for the patients with no positive nodes, 46 % for the patients with one positive node, and 28 % for the patients with two or more positive nodes. CONCLUSIONS: The number of positive lymph nodes predicts survival better than the LNR after resection of extrahepatic cholangiocarcinoma, provided that nodal evaluation is sufficient.

[Signet-Ring Cell Carcinoma of the Ampulla of Vater--Report of a Case].

A 62-year-old man presented with pruritus caused by obstructive jaundice. He was diagnosed with carcinoma of the ampulla of Vater and underwent pylorus-preserving pancreaticoduodenectomy. Histologic examination revealed signet-ring cell carcinoma without nodal metastasis. The patient underwent a partial resection of the small bowel for small bowel obstruction 38 months after the initial resection. Histologic examination disclosed signet-ring cell carcinoma at the surface of the resected small bowel, and the diagnosis of peritoneal recurrence was confirmed. He received oral S-1(100 mg/day) every other day for 14 months until bowel obstruction caused by peritoneal carcinomatosis became apparent. The patient died of the disease 58 months after the initial resection.

[Repeated Pancreatic Resections with Parenchymal Preservation for Pancreatic Metastases of Renal Cell Carcinoma--Report of a Case].

A 51-year-old man underwent right nephrectomy for renal cell carcinoma. Six months later, a solitary metastatic tumor was detected in the pancreatic tail and he underwent distal pancreatectomy and splenectomy. One year and 6 months after the initial resection, a solitary metastatic tumor was detected in the pancreas head, and he underwent partial pancreatectomy. A solitary metastatic tumor was detected again in the remnant pancreatic body 3 years and 10 months after the initial resection. Partial resection of the distal part of the remnant pancreas was performed. The patient remains alive and well with no evidence of remnant disease 4 years after the initial resection.

Risk of subsequent biliary malignancy in patients undergoing cyst excision for congenital choledochal cysts.

BACKGROUND AND AIM: The aim of this study was to elucidate the risk of subsequent biliary malignancy in patients undergoing cyst excision for congenital choledochal cysts. METHODS: A retrospective analysis of 94 patients who had undergone cyst excision for congenital choledochal cysts was conducted. The median age at the time of cyst excision and median follow-up time after cyst excision were 7 years and 181 months, respectively. RESULTS: Biliary tract cancer developed in four patients at 13, 15, 23, and 32 years after cyst excision. The cumulative incidences of biliary tract cancer at 15, 20, and 25 years after cyst excision were 1.6%, 3.9%, and 11.3%, respectively. The sites of biliary tract cancer were the intrahepatic (n = 2), hilar (n = 1), and intrapancreatic (n = 1) bile ducts. Of the four patients with biliary tract cancer after cyst excision, three patients underwent surgical resection and one patient received chemo-radiotherapy. The overall cumulative survival rates after treatment in the four patients with biliary tract cancer were 50% at 2 years and 25% at 3 years, with a median survival time of 15 months. CONCLUSIONS: The risk of subsequent biliary malignancy in patients undergoing cyst excision for congenital choledochal cysts seems to be relatively high in the long-term. The risk of biliary malignancy in the remnant bile duct increases more than 15 years after cyst excision. Despite an aggressive treatment approach for this condition, subsequent biliary malignancy following cyst excision for congenital choledochal cysts shows an unfavorable outcome.

Clinicopathological features of benign biliary strictures masquerading as biliary malignancy.

Discrimination between benign and malignant biliary strictures is difficult, with 5.2 to 24.5 per cent of biliary strictures proving to be benign after histological examination of the resected specimen. This study aimed to evaluate the clinicopathological features of benign biliary strictures in patients undergoing resection for presumed biliary malignancy. From January 1990 to August 2010, 5 of 153 (3.3%) patients who had undergone resection after a preoperative diagnosis of biliary malignancy had a final histological diagnosis of benign biliary stricture. The infiltration of immunoglobulin G4-positive plasma cells was evaluated by immunohistochemistry. None of the five patients had a history of trauma or earlier hepatobiliary surgery and all five underwent hemihepatectomy (combined with extrahepatic bile duct resection in three patients). Postoperative morbidity was recorded in two patients (transient cholangitis and biliary fistula), but there was no postoperative mortality. Histological re-examination identified immunoglobulin G4-related sclerosing cholangitis (n = 2) and nonspecific fibrosis/inflammation (n = 3). No preoperative clinical or radiographic features were identified that could reliably distinguish patients with benign biliary strictures from those with biliary malignancies. Although benign biliary strictures are rare, differentiating benign strictures from malignancy remains problematic. Thus, the treatment approach for biliary strictures should remain surgical resection for presumed biliary malignancy.

"Extended" radical cholecystectomy for gallbladder cancer: long-term outcomes, indications and limitations.

AIM: To delineate indications and limitations for "extended" radical cholecystectomy for gallbladder cancer: a procedure which was instituted in our department in 1982. METHODS: Of 145 patients who underwent a radical resection for gallbladder cancer from 1982 through 2006, 52 (36%) had an extended radical cholecystectomy, which involved en bloc resection of the gallbladder, gallbladder fossa, extrahepatic bile duct, and the regional lymph nodes (first- and second-echelon node groups). A retrospective analysis of the 52 patients was conducted including at least 5 years of follow up. Residual tumor status was judged as no residual tumor (R0) or microscopic/macroscopic residual tumor (R1-2). Pathological findings were documented according to the American Joint Committee on Cancer Cancer Staging Manual (7th edition). RESULTS: The primary tumor was classified as pathological T1 (pT1) in 3 patients, pT2 in 36, pT3 in 12, and pT4 in 1. Twenty-three patients had lymph node metastases; 11 had a single positive node, 4 had two positive nodes, and 8 had three or more positive nodes. None of the three patients with pT1 tumors had nodal disease, whereas 23 of 49 (47%) with pT2 or more advanced tumors had nodal disease. One patient died during the hospital stay for definitive resection, giving an in-hospital mortality rate of 2%. Overall survival (OS) after extended radical cholecystectomy was 65% at 5 years and 53% at 10 years in all 52 patients. OS differed according to the pT classification (P < 0.001) and the nodal status (P = 0.010). All of 3 patients with pT1 tumors and most (29 of 36) patients with pT2 tumors survived for more than 5 years. Of 12 patients with pT3 tumors, 8 who had an R1-2 resection, distant metastasis, or extensive extrahepatic organ involvement died soon after resection. Of the remaining four pT3 patients who had localized hepatic spread through the gallbladder fossa and underwent an R0 resection, 2 survived for more than 5 years and another survived for 4 years and 2 mo. The only patient with pT4 tumor died of disease soon after resection. Among 23 node-positive patients, 11 survived for more than 5 years, and of these, 10 had a modest degree of nodal disease (one or two positive nodes). CONCLUSION: Extended radical cholecystectomy is indicated for pT2 tumors and some pT3 tumors with localized hepatic invasion, provided that the regional nodal disease is limited to a modest degree (up to two positive nodes). Extensive pT3 disease, pT4 disease, or marked nodal disease appears to be beyond the scope of this radical procedure.

Assessment of lymph node status in gallbladder cancer: location, number, or ratio of positive nodes.

UNLABELLED: A BACKGROUND: Assessment of lymph node status is a critical issue in the surgical management of gallbladder cancer. The aim of this study was to compare the anatomical location of positive nodes, number of positive nodes, and lymph node ratio (LNR) as prognostic predictors in gallbladder cancer. METHODS: We conducted a retrospective analysis of 135 patients with gallbladder cancer who underwent a radical resection with regional lymphadenectomy. A total of 2,245 regional lymph nodes were retrieved (median, 14 per patient). The location of positive nodes was classified according to the AJCC staging manual (7th edition). 'Optimal' cutoff values were determined for the number of positive nodes and LNR based on maximal χ(2) scores calculated with the Cox proportional hazards regression model. RESULTS: Lymph node metastasis was found histologically in 59 (44%) patients. The 'optimal' cutoff values for the number of positive nodes and LNR were determined to be three nodes and 10%, respectively. Univariate analysis identified location of positive nodes (pN0, pN1, pN2; P<0.001), number of positive nodes (0, 1 to 3, ≥ 4; P <0.001), and LNR (0%, 0 to 10%, >10%; P<0.001) as significant prognostic factors. Multivariate analysis identified number of positive nodes as an independent prognostic factor ( P=0.004); however, location of positive nodes and LNR failed to remain as an independent variable. CONCLUSIONS: The number of positive lymph nodes better predicts patient outcome after resection than either the location of positive lymph nodes or LNR in gallbladder cancer. Dividing the number of positive lymph nodes into three categories (0, 1 to 3, or ≥ 4) is valid for stratifying patients based on the prognosis after resection.

Impaired olfactory function in mice with allergic rhinitis.

OBJECTIVE: It has been reported that olfactory function is impaired in patients with allergic rhinitis. However, the mechanism of olfactory dysfunction in allergic rhinitis remains poorly understood. Because of difficulties in obtaining and analyzing human olfactory mucosa due to both technical and ethical issues, an animal model needs to be established to clarify the mechanism of olfactory dysfunction in allergic rhinitis. The purpose of this study was to study olfactory function and changes in olfactory mucosa using allergic rhinitis mice. METHODS: A model of allergic rhinitis mice with olfactory dysfunction was developed by sensitizing with ovalbumin (OVA), and intranasally challenging with the same allergen. Olfactory function of mice with or without allergic rhinitis was assessed by odor detection ability test with cycloheximide and local field potential (LFP) with 1-octanal. We also evaluated histological changes in the olfactory mucosa of allergic rhinitis mice by both light and electron microscopy. RESULTS: Both of odor detection ability test and LFP showed that olfactory function was impaired in mice with allergic rhinitis, but not in mice without allergic rhinitis. Histopathological findings showed prominent infiltration of eosinophils, plasma cells, neutrophils, mast cells, and macrophages in lamina propria of olfactory mucosa of mice with allergic rhinitis, although infiltration of these cells was not seen in control mice. Allergic rhinitis also increased the number and size of glands in olfactory mucosa, suggesting an elevated amount of mucin in olfactory mucosa. CONCLUSION: This study showed for the first time that mice with allergic rhinitis have impaired olfactory function, increased size and number of olfactory glands, and infiltration of eosinophils, neutrophils, mast cells, plasma cells, and macrophages in the olfactory mucosa. This suggests that allergic reactions are seen in olfactory mucosa of mice with allergic rhinitis, and that greater olfactory gland activity is associated with olfactory dysfunction. Also, this mouse model could provide an expedient system for analyzing mechanisms of olfactory dysfunction.

Blocking of protease allergens with inhibitors reduces allergic responses in allergic rhinitis and other allergic diseases.

CONCLUSIONS: Allergic responses specific to the corresponding proteases were reduced by protease inhibitors, suggesting promise as potent treatments for allergic rhinitis and other allergic conditions. OBJECTIVE: Allergic diseases, such as allergic rhinitis, are caused by the overproduction of IgE antibodies to various allergens. Many reported allergens are proteases that are cysteine, serine, aspartic (acid) proteases and metalloproteases. Conjugation of E64 inhibitor with cysteine protease allergens inhibits the IgE response to the same allergens. However, whether inhibitors of the other protease families reduce IgE levels and whether protease inhibitors reduce allergic symptoms remain controversial. Therefore, we compared the abilities of active and inhibitor-blocked inactive forms of proteases to generate IgE and allergic symptoms in this study to evaluate associations between the allergic response and protease inhibitors. MATERIALS AND METHODS: We measured levels of IgE, IgG1, IgG2a, and IgG2b enzyme-specific antibodies, and counted frequency of sneezing and nasal rubbing behavior in mice immunized with active or inactive forms of bromelain, chymotrypsin, chymosin and collagenase (a cysteine protease, a serine protease, an aspartic protease and a metalloprotease, respectively). RESULTS: All the inhibitors reduced IgE and IgG1 production in response to corresponding enzymes, and a cysteine protease inhibitor, E64, decreased nasal symptoms, such as sneezing and nasal rubbing.