Continuous glucose monitoring in a patient with insulinoma presenting with unawareness of postprandial hypoglycemia.

Summary: Unawareness of postprandial hypoglycemia for 5 years was identified in a 66-year-old man at a local clinic. The patient was referred to our hospital because of this first awareness of hypoglycemia (i.e. lightheadedness and impaired consciousness) developing after lunch. In a 75 g oral glucose tolerance test, the plasma glucose concentration was decreased to 32 mg/dL (1.8 mmol/L) at 150 min with relatively high concentrations of insulin (8.1 µU/mL), proinsulin (70.3 pmol/L), and C-peptide (4.63 ng/mL). In a prolonged fasting test, the plasma glucose concentration was decreased to 43 mg/dL (2.4 mmol/L) at 66 h with an insulin concentration of 1.4 µU/mL and a C-peptide concentration of 0.49 ng/mL. Computed tomography showed an 18 mm hyperenhancing tumor in the uncinate process of the pancreas. A selective arterial calcium stimulation test showed an elevated serum insulin concentration in the superior mesenteric artery. The patient was then diagnosed with insulinoma and received pancreaticoduodenectomy. Continuous glucose monitoring (CGM) using the Dexcom G6 system showed unawareness of hypoglycemia mainly during the daytime before surgery. When the sensor glucose value was reduced to 55 mg/dL (3.1 mmol/L), the Dexcom G6 system emitted an urgent low glucose alarm to the patient four times for 10 days. Two months after surgery, an overall increase in daily blood glucose concentrations and resolution of hypoglycemia were shown by CGM. We report a case of insulinoma with unawareness of postprandial hypoglycemia in the patient. The Dexcom G6 system was helpful for assessing preoperative hypoglycemia and for evaluating outcomes of treatment by surgery. Learning points: Insulinoma occasionally leads to postprandial hypoglycemia. The CGM system is useful for revealing the presence of unnoticed hypoglycemia and for evaluating treatment outcomes after surgical resection. The Dexcom G6 system has an urgent low glucose alarm, making it particularly suitable for patients who are unaware of hypoglycemia.

Gastrocolic fistula caused by transverse colon cancer: a case report.

BACKGROUND: A gastrocolic fistula is an unusual communication between the colon and the stomach. Although colon cancer is the most common malignant cause of gastrocolic fistula in the Western world, the incidence of gastrocolic fistula due to colon cancer is 0.3% in operated cases. CASE PRESENTATION: A 68-year-old man presented with anorexia, general malaise, weight loss, and vomiting of fecal matter. Investigations revealed that the patient had a large nonmetastatic splenic flexure tumor that was diagnosed as colon cancer and had invaded the stomach and pancreas. An upper gastrointestinal series confirmed a gastrocolic fistula. Left hemicolectomy, distal gastrectomy, distal pancreatectomy, and splenectomy were performed. Histology revealed transverse colon cancer, which was UICC stage (8th edition) pT4bN1bcM0 pStage IIIC. Adjuvant chemotherapy was not performed. There was no recurrence or metastasis one year after surgery. We reviewed 17 cases including our case of a gastrocolic fistula caused by colon cancer. Neoadjuvant chemotherapy was not given to any of the patients, and en bloc resections were conducted in all cases. Adjuvant chemotherapy was given to almost all of the patients. There was no recurrence or metastasis. CONCLUSIONS: For gastrocolic fistula caused by advanced colon cancer, secure en bloc surgical resection was the initial treatment in all 17 reported cases including the present case, and adjuvant chemotherapy may contribute to a better prognosis.

Recurrent distal cholangiocarcinoma and humoral hypercalcemia of malignancy: report of a rare case and literature review.

A 61-year-old Japanese woman presented with epigastric pain and jaundice. Imaging showed the presence of primary distal cholangiocarcinoma (DCC). A subtotal stomach-preserving pancreaticoduodenectomy was performed, followed by chemotherapy using S-1. However, second-line chemotherapy with gemcitabine and cis-diamminedichloroplatinum was required for the treatment of hepatic metastasis of the DCC 3 months following the surgery. Nine months after the surgery, the serum calcium and parathyroid hormone-related peptide concentrations were high, at 16.5 mg/dL and 28.7 pmol/L, respectively, which suggested the presence of humoral hypercalcemia of malignancy (HHM) secondary to the DCC. Moreover, marked leukocytosis, with a white blood cell count of 40,400/µL, was also present. The patient died 11 months after the diagnosis of DCC. Because hypercalcemia of malignancy is associated with a poor prognosis, and HHM and leukocytosis caused by DCC are very rare, we have presented the present case in detail and provide a review of the existing literature.

Application of a novel surgical difficulty grading system during laparoscopic cholecystectomy.

BACKGROUND: Prevention of bile duct injury and vasculo-biliary injury while performing laparoscopic cholecystectomy (LC) is an unsolved problem. Clarifying the surgical difficulty using intraoperative findings can greatly contribute to the pursuit of best practices for acute cholecystitis. In this study, multiple evaluators assessed surgical difficulty items in unedited videos and then constructed a proposed surgical difficulty grading. METHODS: We previously assembled a library of typical video clips of the intraoperative findings for all LC surgical difficulty items in acute cholecystitis. Fifty-one experts on LC assessed unedited surgical videos. Inter-rater agreement was assessed by Fleiss's κ and Gwet's agreement coefficient (AC). RESULTS: Except for one item ("edematous change"), κ or AC exceeded 0.5, so the typical videos were judged to be applicable. The conceivable surgical difficulty gradings were analyzed. According to the assessment of difficulty factors, we created a surgical difficulty grading system (agreement probability = 0.923, κ = 0.712, 90% CI: 0.587-0.837; AC2  = 0.870, 90% CI: 0.768-0.972). CONCLUSION: The previously published video clip library and our novel surgical difficulty grading system should serve as a universal objective tool to assess surgical difficulty in LC.

National survey of hepatobiliary and pancreatic surgery in hemophilia patients in Japan.

BACKGROUND: Approximately 8300 hemophiliacs are registered in Japan, but no comprehensive reports on hepatobiliary and pancreatic surgery (HBPS) have been conducted. This report investigates the current status of HPBS in hemophilia patients in Japan. METHODS: The subjects were hemophiliac patients seen between January 1 2007, and December 31 2017, at facilities participating in this study among the facilities for performing high-difficulty cases nationwide designated by the Japanese Society for HBPS. A retrospective examination of short-term outcomes in 49 cases was conducted to assess patient background, disease, surgical procedure, and complications. RESULTS: The types of hemophilia were A: 43 cases, B: four cases, and von Willebrand disease: two cases (hemophilia severity: mild 32, moderate seven, severe 10). The target malignant diseases for surgery were hepatocellular carcinoma (HCC) in 20 cases, intrahepatic cholangiocellular carcinoma (CCC) in four cases, combined HCC-CCC in two cases, hilar CCC in two cases, and pancreatic cancer in four cases. As for the surgical procedure, limited resection (subsegmentectomy and partial hepatectomy) was performed in 16 cases of HCC even with normal liver function tests. Pancreaticoduodenectomy and distal pacreatectomy were performed for pancreatic cancers as in the standard procedure. Postoperative complications were postoperative bleeding in two cases after hepatectomy and one after pancreatectomy in one case. When compared with Japanese National Clinical Data base, the complication rates after hepatectomy and pancreatectomy were not conspicuous in hemophilic patients. CONCLUSIONS: As long as they are performed in qualified centers, complication rate is not increased in hemophilic patients undergoing HBPS.

Assembling a library of typical surgery video clips to construct a system for assessing the surgical difficulty of laparoscopic cholecystectomy.

BACKGROUND: To explore best practices for acute cholecystitis, it is necessary to construct a system to assess the difficulty of laparoscopic cholecystectomy (LC) based on intraoperative findings. In this study, multiple evaluators assessed videos of LC to assemble a library of typical video clips for 25 intraoperative findings. METHODS: We have previously identified 25 items that contribute to surgical difficulty in LC. For each item, roughly 30-second video clips were submitted from videos of LC performed at member institutions. We then selected one typical video from the collected clips based on simple tabulation of the instances of agreement. Inter-rater agreement was assessed with Fleiss's κ and Gwet's agreement coefficient (AC). RESULTS: Except in the case of two assessment items ("edematous change" and "easy bleeding"), κ or AC significantly exceeded 0.5 and the typical videos were judged to be applicable. For the two remaining items, the evaluation was repeated after clarifying the definitions of positive and negative findings. Eventually, they were recognized as typical. The completed video clip library contains 31 clips and is divided into five categories (http://www.jshbps.jp/modules/project/index.php?content_id=13). CONCLUSIONS: This clip library may be highly useful in clinical settings as a more objective standard for assessing surgical difficulty in LC.

A multicenter prospective registration study on laparoscopic pancreatectomy in Japan: report on the assessment of 1,429 patients.

BACKGROUND: Prospective studies are needed to understand the safety and feasibility of laparoscopic pancreatectomy. The aim of the present study was to describe laparoscopic pancreatectomy currently undertaken in Japan, using a prospective registration system. METHODS: Patient characteristics and planned operations were registered preoperatively, and then the performed operation and outcomes were reported using an online system. Collected data were also compared between institutions based on their level of experience. This study was registered with UMIN000022836. RESULTS: Available data were obtained from 1,429 patients at 100 Japanese institutions, including 1,197 laparoscopic distal pancreatectomies (LDPs) and 232 laparoscopic pancreatoduodenectomies (LPDs). The rates of completion for planned operations were 92% for LDP and 91% for LPD. Postoperative complication rates after LDP and LPD were 17% and 30%, and 90-day mortality rates were 0.3% and 0.4%, respectively. Shorter operation time, less blood loss, and lower incidence of pancreatic fistula were observed in institutions experienced in LDP. A higher rate of pure laparoscopic procedure and shorter operation time were noted in institutions experienced with LPD. CONCLUSION: LDPs and LPDs are performed safely in Japan, especially in experienced institutions. Our data could support the next challenges in the field of laparoscopic pancreatectomy.

Pure laparoscopic right posterior sectionectomy using the caudate lobe-first approach.

BACKGROUND: In our process of standardizing laparoscopic right-sided anatomical hepatectomy, we found several advantages of the caudate lobe-first approach. We herein describe our standardized procedure of laparoscopic right posterior sectionectomy (Lap-RPS) using this approach. METHODS: Between January 2011 and January 2018, 31 patients underwent pure Lap-RPS in our hospital. The mean patient age was 68 years (range 47-85 years), and the number of male patients was more than that of female patients (64.5%). Of 31 patients, 20 had metastatic liver tumor, 7 had hepatocellular carcinoma, 3 had intrahepatic cholangiocellular carcinoma, and 1 had hemangioma. All 31 patients had Child-Pugh class A liver function. The surgical technique was recorded on video. Cumulative sum (CUSUM) analyses were applied to assess the learning curve. RESULTS: The mean operative time was 420 min (range 263-639 min), and the mean amount of blood loss was 304 g (range 10-900 g). No procedure was converted to open surgery. Postoperative bleeding, bile leakage, hepatic failure, and mortality did not occur. CUSUM analyses showed a decrease in the operative time and blood loss after using the caudate lobe-first approach. CONCLUSION: Our standardized procedure of Lap-RPS using the caudate lobe-first approach is not only feasible but also expected to provide an advantage for laparoscopic anatomical hepatectomy.

Recurrent renal cell carcinoma leading to a misdiagnosis of polycystic liver disease: A case report.

BACKGROUND: Polycystic liver disease (PCLD) with a large cystic volume deteriorates the quality of life of patients through substantial effects on the adjacent organs, recurrent cyst infections, cyst rupture, and hemorrhage. Surgical or radiological intervention is usually needed to alleviate these symptoms. We report a rare case of the cystic metastasis of renal cell carcinoma (RCC), which was misdiagnosed as PCLD, as a result of the clinical and radiological similarity between these disorders. CASE SUMMARY: A 74-year-old female who had undergone nephrectomy for papillary-type RCC (PRCC) was suffering from abdominal pain and the recurrent intracystic hemorrhage of multiple cysts in the liver. Imaging studies and aspiration cytology of the cysts showed no evidence of malignancy. With a diagnosis of autosomal dominant polycystic liver disease, the patient received hepatectomy for the purpose of mass reduction and infectious cyst removal. Surgery was performed without complications, and the patient was discharged on postoperative day 14. Postoperatively, the pathology revealed a diagnosis of recurrent PRCC with cystic formation. CONCLUSION: This case demonstrates the importance of excluding the cystic metastasis of a cancer when liver cysts are observed.

Decreased serum carbohydrate antigen 19-9 levels after neoadjuvant therapy predict a better prognosis for patients with pancreatic adenocarcinoma: a multicenter case-control study of 240 patients.

BACKGROUND: Carbohydrate antigen (CA) 19-9 levels after resection are considered to predict prognosis; however, the significance of decreased CA19-9 levels after neoadjuvant therapy has not been clarified. This study aimed to define the prognostic significance of decreased CA19-9 levels after neoadjuvant therapy in patients with pancreatic adenocarcinoma. METHODS: Between 2001 and 2012, 240 consecutive patients received neoadjuvant therapy and subsequent resection at seven high-volume institutions in Japan. These patients were divided into three groups: Normal group (no elevation [≤37 U/ml] before and after neoadjuvant therapy), Responder group (elevated levels [> 37 U/ml] before neoadjuvant therapy but decreased levels [≤37 U/ml] afterwards), and Non-responder group (elevated levels [> 37 U/ml] after neoadjuvant therapy). Analyses of overall survival and recurrence patterns were performed. Uni- and multivariate analyses were performed to clarify the clinicopathological factors influencing overall survival. The initial metastasis sites were also evaluated in these groups. RESULTS: The Responder group received a better prognosis than the Non-responder group (3-year overall survival: 50.6 and 41.6%, respectively, P = 0.026), but the prognosis was comparable to the Normal group (3-year overall survival: 54.2%, P = 0.934). According to the analysis of the receiver operating characteristic curve, the CA19-9 cut-off level defined as no elevation after neoadjuvant therapy was ≤103 U/ml. The multivariate analysis revealed that a CA19-9 level ≤ 103 U/ml, (P = 0.010, hazard ratio: 1.711; 95% confidence interval: 1.133-2.639), tumor size ≤27 mm (P = 0.040, 1.517; (1.018-2.278)), a lack of lymph node metastasis (P = 0.002, 1.905; (1.276-2.875)), and R0 status (P = 0.045, 1.659; 1.012-2.627) were significant predictors of overall survival. Moreover, the Responder group showed a lower risk of hepatic recurrence (18%) compared to the Non-responder group (31%), though no significant difference in loco-regional, peritoneal or other distant recurrence were observed between groups (P = 0.058, P = 0.700 and P = 0.350, respectively). CONCLUSIONS: Decreased CA19-9 levels after neoadjuvant therapy predicts a better prognosis, with low incidence of hepatic recurrence after surgery.

Sustained Elevation of Postoperative Serum Level of Carbohydrate Antigen 19-9 is High-Risk Stigmata for Primary Hepatic Recurrence in Patients with Curatively Resected Pancreatic Adenocarcinoma.

BACKGROUND: Survival after surgery for pancreatic adenocarcinoma (PA) is poor and heterogeneous, even for curative (R0) resection. Serum carbohydrate antigen (CA) 19-9 levels are important prognostic markers for resected PA. However, sustained elevation of CA19-9 in association with the patterns of recurrence has been rarely investigated. METHODS: Patients who underwent R0 resection (n = 539) were grouped according to postoperative serum CA19-9 levels (Group E: sustained elevation; Group N: no elevation). Clinicopathological factors, patterns of recurrence, and survival were compared between the groups. RESULTS: Group E (n = 159) had significantly shorter median overall survival (17.1 vs. 35.4 months, p < 0.0001) than Group N (n = 380). Postoperative CA19-9 elevation was a significant independent predictor of poor survival in multivariate analysis (hazard ratio 1.98, p < 0.0001). The rate of hepatic recurrence in Group E was 2.6-fold higher than in Group N (45% vs. 17%, p < 0.0001). Postoperative CA19-9 elevation was a strongest independent predictor of primary hepatic recurrence (p < 0.0001) by a multiple regression model. Loco-regional, peritoneal, and other distant recurrence did not differ between the groups. The extent of preoperative CA19-9 elevation was correlated sustained elevation of CA19-9 after surgery (p < 0.0001) and primary hepatic recurrence (p = 0.0019). CONCLUSIONS: Sustained CA19-9 elevation was strong predictor of primary hepatic recurrence and short survival in cases of R0 resection for PA.

Indocyanine green fluorescence-navigated laparoscopic metastasectomy for peritoneal metastasis of hepatocellular carcinoma: a case report.

BACKGROUND: Indocyanine green (ICG) can selectively accumulate in primary hepatocellular carcinoma (HCC) and its extrahepatic metastases. ICG fluorescence imaging is an extremely sensitive intraoperative tool for detecting HCC foci and can be used to detect impalpable tumors in laparoscopic surgery. Here, we report a case of a 75-year-old man who underwent peritoneal metastasis resection of HCC using a laparoscopic near-infrared imaging system and ICG fluorescence-navigated surgery. CASE PRESENTATION: A 75-year-old man was referred to our department for peritoneal metastasis resection of HCC. Two years before admission, he had undergone transarterial embolization and segmentectomy of segment 6 with open surgery for ruptured HCC. Computed tomography revealed a 12-mm peritoneal metastatic lesion on the abdominal wall near the cut surface of the liver. No other metastases were observed; resection of the solitary metastasis was scheduled. ICG (0.5 mg/kg body weight) was intravenously injected, 72 h preoperatively. An endoscopic, ICG near-infrared fluorescence imaging system revealed clear green fluorescence, indicating peritoneal metastasis of HCC on the abdominal wall. The tumor was resected with adequate surgical margin by partially resecting the liver and diaphragm, followed by histological confirmation as peritoneal metastasis of HCC. No recurrence was observed after 12 months of follow-up. CONCLUSIONS: ICG fluorescence can be useful in laparoscopic surgery for identifying peritoneal metastasis.

Surgical resection of hepatic and rectal metastases of pancreatic acinar cell carcinoma (PACC): a case report.

BACKGROUND: Pancreatic acinar cell carcinoma (PACC), a rare variant of pancreatic malignancy, is generally managed the same way as pancreatic ductal adenocarcinoma (PDAC). Surgical resection is the gateway to curing it; however, once it metastasizes (usually to the liver, lungs, lymph nodes, or peritoneal cavity), systemic chemotherapy has been the only option, but with unfavorable results. CASE PRESENTATION: A 67-year-old man with symptoms of loss of appetite and weight underwent surgery for malignancy of the pancreatic tail extending into the entire pancreas. The pathological diagnosis was PACC following total pancreatectomy. Twenty-four months after the pancreatectomy, a solitary liver metastasis was treated by partial hepatectomy, and, subsequently, 4 months later, he presented with melena. Further examination revealed a type-2 rectal tumor. Histological examination following biopsy revealed it to be rectal metastasis of PACC, and it was treated by abdominoperineal resection. Subsequently, the patient did not have tumor recurrence as of 40 months after pancreatectomy. CONCLUSIONS: This is a rare case of PACC presenting with metachronal metastases in the liver and rectum, and we successfully treated them by surgical resections. Since the malignant behavior of PACC is usually less than that of PDAC, surgical resection could be an option even for metastatic lesions when the number and extent of metastases are limited.

Pure laparoscopic right hemihepatectomy using the caudodorsal side approach (with videos).

BACKGROUND: In our process of standardizing laparoscopic right hemihepatectomy (Lap-RH), we found several advantages of the laparoscopic caudate lobe first approach by using a unique laparoscopic caudodorsal view. METHODS: Between April 2012 and October 2017, 21 patients underwent pure Lap-RH at our hospital. The mean patient age was 62 years (range 36-75 years), and there were more male than female patients (66.7%). Of 21 patients, 11 had hepatocellular carcinoma, eight had metastatic tumor, and the other two had focal nodular hyperplasia and refractory liver abscess. All 21 patients had Child-Pugh class A liver function. The surgical technique was recorded on video. RESULTS: The mean operative time was 409 min (range 241-522 min), and the mean blood loss was 279 g (range 0-1,010 g). No procedure was converted to open surgery. With regard to postoperative complications, one patient had bile leakage from the stump of the main Glissonean branch and another patient had abscess formation in the subphrenic space. No postoperative bleeding, hepatic failure, and mortality occurred. CONCLUSIONS: Our standardized procedure of Lap-RH using the unique laparoscopic caudodorsal view is not only feasible but also confers a true advantage of the laparoscopic approach.

Perioperative and oncological outcomes of laparoscopic anatomical hepatectomy for hepatocellular carcinoma introduced gradually in a single center.

BACKGROUND: Anatomical hepatectomy is an ideal curative treatment for hepatocellular carcinoma (HCC). We have standardized our laparoscopic anatomical hepatectomy (LAH) procedure, gradually extending its indications. In the present study, we describe our experience and the perioperative and oncological outcomes of LAH for HCC compared to those of open anatomical hepatectomy (OAH) during the gradual introduction of LAH. METHODS: Seventy patients with primary HCC underwent anatomical hepatectomy in our institution from November 2008 to April 2014. As we gained experience with LAH, our indications for choosing LAH over OAH gradually expanded. Ultimately, 40 and 30 patients underwent LAH and OAH, respectively. Perioperative and oncological outcomes were compared between the two groups. RESULTS: There were no significant differences in age, sex, background of liver disease, liver function, tumor size, tumor number, or type of liver resection between the two groups. Major complications and mortality rates were similar between the LAH and OAH groups (12.5% vs. 20%; p = 0.582, and 0% vs. 3.3%; p = 0.429, respectively). The median follow-up time after surgery was 40.5 months in the LAH group and 32.9 months in the OAH group (p = 0.835). The 1-, 3-, and 5-year overall survival rates were 89.9, 84.7, and 70.9%, in the LAH group, and 89.8, 68.0, and 63.1% in the OAH group, respectively (p = 0.255). The 1-, 3-, and 5-year disease-free survival rates were 79.5, 58.0, and 42.5%, in the LAH group, and 72.4, 56.1, and 50.4% in the OAH group, respectively (p = 0.980). CONCLUSIONS: Through gradual introduction of LAH, we obtained comparable results to those achieved with OAH. LAH can be a feasible surgical treatment for primary HCC, with good oncological outcomes.

Is distal pancreatectomy with en-bloc celiac axis resection effective for patients with locally advanced pancreatic ductal adenocarcinoma? -Multicenter surgical group study.

OBJECTIVES: We retrospectively investigated the operative outcomes of patients who underwent distal pancreatectomy (DP) for invasive pancreatic ductal adenocarcinoma (PDAC) located at the body and tail. METHODS: Data from 395 patients with PDAC who underwent DP with margin-negative resection (R0 or R1) were collected from seven high-volume centers in Japan from 2001 to 2012. Among them, 72 patients underwent DP with en-bloc celiac axis resection (DP-CAR). The remaining 323 patients underwent conventional DP with splenectomy (DP-S). To determine the efficacy of DP-CAR, clinicopathological data were compared between the DP-CAR and the DP-S groups. RESULTS: The DP-S group consisted mainly of patients with resectable disease (93%), and conversely, all patients in the DP-CAR group had borderline resectable or unresectable disease. The overall morbidity was significantly higher in the DP-CAR group than in the DP-S group (63% vs 47%, respectively; P = 0.017). The median survival time (MST) of the DP-CAR group was significantly shorter than that of the DP-S group (17.5 vs 28.6 months, respectively; P = 0.004). However, the MST of patients in the DP-CAR group (n = 61, 85%) who received adjuvant therapy was significantly longer than that of patients in the DP-S group (n = 65, 20%) who underwent R1 resection (21.9 vs 16.7 months, respectively; P = 0.024). CONCLUSION: DP-CAR followed by adjuvant chemotherapy provided an acceptable overall survival rate in patients with highly advanced PDAC, but should be performed with great caution because of high morbidity. Patients with a high risk of positive surgical margins with DP-S may be candidates for DP-CAR.

Gallbladder bleeding associated with microscopic polyangiitis: a case report.

A 71-year-old male who had a 6 years history of microscopic polyangiitis (MPA) was admitted to our hospital with a chief complaint of upper abdominal pain and nausea. Abdominal contrast-enhanced CT revealed extravasation of contrast medium in the gallbladder, and the patient was diagnosed with gallbladder bleeding. Although we started conservative treatment, anemia, hypotension and tachycardia had progressed gradually. Therefore, we performed emergent laparoscopic cholecystectomy on the following day. Intraoperative findings showed a remarkably distended gallbladder due to interior clots; however, the cholecystitis itself was not significant. Histopathological findings showed infiltrations of inflammatory cells around the blood vessels and vascular rupture. The postoperative course was uneventful. MPA is a type of ANCA-associated vasculitis. To the best of our knowledge, this is the first report of gallbladder bleeding associated with MPA. Spontaneous hemostasis cannot be expected, instead, surgical treatment must be performed promptly.

Retrospective Study of the Correlation Between Pathological Tumor Size and Survival After Curative Resection of T3 Pancreatic Adenocarcinoma: Proposal for Reclassification of the Tumor Extending Beyond the Pancreas Based on Tumor Size.

BACKGROUND: Even though most patients who undergo resection of pancreatic adenocarcinoma have T3 disease with extra-pancreatic tumor extension, T3 disease is not currently classified by tumor size. The aim of this study was to modify the current TNM classification of pancreatic adenocarcinoma to reflect the influence of tumor size. METHODS: A total of 847 consecutive pancreatectomy patients were recruited from multiple centers. Optimum tumor size cutoff values were calculated by receiver operating characteristics analysis for tumors limited to the pancreas (T1/2) and for T3 tumors. In our modified TNM classification, stage II was divided into stages IIA (T3aN0M0), IIB (T3bN0M0), and IIC (T1-3bN1M0) using tumor size cutoff values. The usefulness of the new classification was compared with that of the current classification using Akaike's information criterion (AIC). RESULTS: The optimum tumor size cutoff value distinguishing T1 and T2 was 2 cm, while T3 was divided into T3a and T3b at a tumor size of 3 cm. The median survival time of the stages IIA, IIB, and IIC were 44.7, 27.6, and 20.3 months, respectively. There were significant differences of survival between stages IIA and IIB (P = 0.02) and between stages IIB and IIC (P = 0.03). The new classification showed better performance compared with the current classification based on the AIC value. CONCLUSIONS: This proposed new TNM classification reflects the influence of tumor size in patients with extra-pancreatic tumor extension (T3 disease), and the classification is useful for predicting mortality.

A case of annular pancreas with Wirsung's duct encircling the duodenum: embryological hypothesis based on cholangiopancreatographic and immunohistochemical findings.

We present a resected case of annular pancreas in which Wirsung's duct encircled the duodenum and continued directly to the main pancreatic duct in the body and tail. Furthermore, Wirsung's duct coursed along the right side of the lower bile duct near the major duodenal papilla. Histologically, the islets of Langerhans in the annular pancreas were irregular in shape and were characterized by a striking abundance of pancreatic polypeptide (PP)-positive cells. The PP-rich area that encircled the duodenum was fused with the PP-poor area in the head of the pancreas. The following embryological hypothesis is proposed. The tip of the ventral pancreatic anlage adhered to the duodenal wall and stretched to form a ring during clockwise rotation. The rotation was incomplete, and the pancreatic duct did not cross over the lower bile duct. Since there was adequate ventral anlage in the lower part of the head of the pancreas, fusion between the ducts of the ventral and dorsal anlagen did not occur. The tip of the ventral anlage overgrew and adhered to the dorsal anlage, and the annular duct fused with the main duct of the dorsal anlage.

Multicenter Phase II Study of Intravenous and Intraperitoneal Paclitaxel With S-1 for Pancreatic Ductal Adenocarcinoma Patients With Peritoneal Metastasis.

OBJECTIVE: To evaluate the clinical efficacy and tolerability of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel combined with S-1, "an oral fluoropyrimidine derivative containing tegafur, gimestat, and otastat potassium" in chemotherapy-naive pancreatic ductal adenocarcinoma (PDAC) patients with peritoneal metastasis. BACKGROUND: PDAC patients with peritoneal metastasis (peritoneal deposits and/or positive peritoneal cytology) have an extremely poor prognosis. An effective treatment strategy remains elusive. METHODS: Paclitaxel was administered i.v. at 50 mg/m and i.p. at 20 mg/m on days 1 and 8. S-1 was administered at 80 mg/m/d for 14 consecutive days, followed by 7 days of rest. The primary endpoint was 1-year overall survival (OS) rate. The secondary endpoints were antitumor effect and safety (UMIN000009446). RESULTS: Thirty-three patients who were pathologically diagnosed with the presence of peritoneal dissemination (n = 22) and/or positive peritoneal cytology (n = 11) without other organ metastasis were enrolled. The tumor was located at the pancreatic head in 7 patients and the body/tail in 26 patients. The median survival time was 16.3 (11.47-22.57) months, and the 1-year survival rate was 62%. The response rate and disease control rate in assessable patients were 36% and 82%, respectively. OS in 8 patients who underwent conversion surgery was significantly higher than that of nonsurgical patients (n = 25, P = 0.0062). Grade 3/4 hematologic toxicities occurred in 42% of the patients and nonhematologic adverse events in 18%. One patient died of thrombosis in the superior mesenteric artery. CONCLUSIONS: This regimen has shown promising clinical efficacy with acceptable tolerability in chemotherapy-naive PDAC patients with peritoneal metastasis.