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.

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.

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.

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.

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.

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.

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.

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.

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.

[COMPUTER-ASSISTED SURGERY SIMULATING THE PROCESS OF HEPATECTOMY].

In the last five years, many hospitals in Japan have created three-dimensional (3D) images from computed tomography (CT) data from patients who have undergone liver resection to share the images of liver structures with the surgical team and analyze the liver volume based on portal perfusion. However, using the previous software packages, the 3D liver model was fixed and rigid. Therefore, we developed novel 3D simulation software, called Liversim, to visualize real-time malformations of the liver. There were no marked differences during the process of liver resection between Liversim and actual surgery. Virtual liver resection showing real-time malformations of the liver using Liversim is useful for the safe performance of liver resections.

An Experimental Study on the Relationship Among Airway Pressure, Pneumoperitoneum Pressure, and Central Venous Pressure in Pure Laparoscopic Hepatectomy.

OBJECTIVES: To determine optimal settings for airway pressure (AWP), pneumoperitoneum pressure (PPP), and central venous pressure (CVP) in pure laparoscopic hepatectomy. BACKGROUND: High PPP is often employed to control bleeding from the hepatic vein during pure laparoscopic hepatectomy; however, there is a risk of pulmonary gas embolism. We noted that decreases in AWP were often effective. METHODS: After establishing carbon dioxide pneumoperitoneum in 6 male piglets and maintaining PPP at 25 mmHg, CVP was measured 3 times at each of 9 levels of airway pressure, which was increased in increments of 5 cmH2O from 0 to 40 cmH2O. CVP was measured in the same manner by maintaining PPP at 20, 15, 10, 5, and 0 mmHg, and in laparotomy. Correlation and regression analyses were performed among airway pressure, CVP, and pneumoperitoneum pressure. RESULTS: Positive correlations were observed between AWP and CVP and between PPP and CVP (P < 0.001). Under high airway pressure, CVP was persistently higher than pneumoperitoneum pressure. Under low airway pressure, CVP did not increase or often decreased when PPP was higher than CVP. CONCLUSIONS: By increasing pneumoperitoneum pressure, bleeding from the hepatic vein cannot be controlled under high airway pressure, but can be controlled under low airway pressure. However, under low airway pressure, the risk of pulmonary gas embolism increases when PPP is higher than CVP. We consider that reducing AWP is also effective for controlling bleeding from the hepatic vein and safer than increasing pneumoperitoneum pressure.

[Neoadjuvant Chemotherapy Using S-1 for Pancreatic Cancer - Mid-Term Results].

BACKGROUND: Although surgical resection is the only curative strategy for pancreatic cancer, the prognosis of patients with pancreatic cancer remains poor. Recently, neoadjuvant treatment has been frequently employed as a promising treatment. Here, the mid-term results of neoadjuvant chemoradiotherapy(NACRT)using S-1, which has been performed in our hospital since 2008, are reported. METHODS: Seventy-nine patients with resectable or borderline resectable pancreatic ductal adenocarcinoma, who had been intended to undergo NACRT treatment using S-1, were enrolled. The NACRT comprised radiotherapy( 1.8 Gy×28 days)and full-dose twice-daily oral S-1 given on the same days as the radiotherapy. The results of the NACRT and pancreatectomy and the patients' prognoses were evaluated. RESULTS: Fifty-five patients(69.6%)underwent pancreatectomy, with no case of mortality. The curative resection rate was 94.5%. Postoperative adjuvant chemotherapy was administered in 46 patients(83.6%). The 3-year survival rates of all 79 patients and 55 pancreatectomy patients were 40.1% and 50.4%, respectively. CONCLUSION: NACRT using S-1 was found to be feasible, and good mid-term outcomes were obtained. However, analysis of the long-term outcomes and comparisons with other novel anti-cancer drugs are still required.

[A case of hemorrhagic cholecystitis associated with Churg-Strauss syndrome].

A woman in her 70s with Churg-Strauss syndrome presented with epigastric pain. She was being treated with steroids at the time of admission. Computed tomography showed swelling of the gallbladder, and percutaneous transhepatic cholangiography revealed bloody secretion. On duodenoscopy, bleeding was observed from the orifice of the major duodenal papilla. Emergency cholecystectomy was performed under a diagnosis of hemorrhagic cholecystitis;intraoperatively, extensive hematoma was detected in the thickened wall of the gallbladder. Subsequent histopathological examination revealed mucosal ulceration with infiltration of inflammatory cells, torn small vessels, and extensive transmural bleeding and abscess formation in the thickened wall of the gallbladder. We considered that the hemorrhagic cholecystitis was induced by either vasculitis or corticosteroid therapy. To the best of our knowledge, this is the first report of hemorrhagic cholecystitis associated with Churg-Strauss syndrome.

Impact of Preoperative Biliary Drainage on Long-Term Survival in Resected Pancreatic Ductal Adenocarcinoma: A Multicenter Observational Study.

BACKGROUND: This study aimed to evaluate the impact of preoperative biliary drainage (PBD) on the long-term survival of patients with pancreatic ductal adenocarcinoma (PDAC) who underwent pancreaticoduodenectomy (PD). METHODS: A multicenter observational study was performed using a common database of patients with resected PDAC from seven high-volume surgical institutions in Japan. RESULTS: Of 932 patients who underwent PD for PDAC, 573 (62 %) underwent PBD, including 407 (44 %) who underwent endoscopic biliary drainage (EBD) and 166 (18 %) who underwent percutaneous transhepatic biliary drainage (PTBD). The patients who did not undergo PBD and those who underwent EBD had a significantly better overall survival than those who underwent PTBD, with median survival times of 25.7 months (P < 0.001), 22.3 months (P = 0.001), and 16.7 months, respectively. Multivariate analysis showed that seven clinicopathologic factors, including the use of PTBD but not EBD, were independently associated with poorer overall survival. Furthermore, patients who underwent PTBD more frequently experienced peritoneal recurrence (23 %) than those who underwent EBD (10 %; P < 0.001) and those who did not undergo PBD (11 %; P = 0.001). Multivariate analysis demonstrated that the independent risk factors for peritoneal recurrence included surgical margin status (P < 0.001) and use of PTBD (P = 0.004). CONCLUSIONS: Use of PTBD, but not EBD, was associated with a poorer prognosis, with an increased rate of peritoneal recurrence among patients who underwent PD for PDAC.

Proposed preoperative risk factors for early recurrence in patients with resectable pancreatic ductal adenocarcinoma after surgical resection: A multi-center retrospective study.

BACKGROUND/OBJECTIVE: Although surgical resection remains the only chance for cure in patients with pancreatic ductal adenocarcinoma (PDAC), postoperative early recurrence (ER) is frequently encountered. The purpose of this study is to determine the preoperative predictive factors for ER after upfront surgical resection. METHODS: Between 2001 and 2012, 968 patients who underwent upfront surgery with R0 or R1 resection for PDAC at seven high-volume centers in Japan were retrospectively reviewed. ER was defined as relapse within 6 months after surgery. Study analysis stratified by resectable (R) and borderline resectable (BR) PDACs was conducted according to the National Comprehensive Cancer Network guidelines. RESULTS: ER occurred in 239 patients (25%) with a median survival time (MST) of 8.8 months. Modified Glasgow prognostic score = 2 (odds ratio (OR) 2.06, 95% confidence interval (CI) 1.05-3.95; P = 0.044), preoperative CA19-9 ≥300 U/ml (OR 1.94, 1.29-2.90; P = 0.003), and tumor size ≥30 mm (OR 1.72, 1.16-2.56; P = 0.006), were identified as preoperative independent predictive risk factors for ER in patients with R-PDAC. In the R-PDAC patients, MST was 35.5, 26.3, and 15.9 months in patients with 0, 1 and ≥2 risk factors, respectively. There were significant differences in overall survival between the three groups (P < 0.001). No preoperative risk factors were identified in BR-PDAC patients with a high rate of ER (39%). CONCLUSIONS: There is a high-risk subset for ER even in patients with R-PDAC and a simple risk scoring system is useful for prediction of ER.

National Comprehensive Cancer Network Resectability Status for Pancreatic Carcinoma Predicts Overall Survival.

BACKGROUND: The aim of this study was to evaluate the validity of preoperative resectability status, as defined by the National Comprehensive Cancer Network (NCCN), from the viewpoint of overall survival. METHODS: A total of consecutive 704 patients with pancreatic head carcinoma who underwent pancreatoduodenectomy with upfront surgery at seven Japanese hospitals between 2001 and 2012 were evaluated retrospectively. According to the NCCN definition of preoperative resectability status, tumors were divided into resectable tumors without vascular contact (R group), resectable tumors with portal or superior mesenteric vein (PV/SMV) contact of ≦180° (R-PV group), borderline resectable(BR) tumors with PV/SMV contact of >180° (BR-PV group), and BR tumors with arterial contact (BR-A group). The relationship between the NCCN definition of preoperative resectability status and overall survival was analyzed. RESULTS: Of the 704 patients, 389, 114, 145, and 56 were classified into the R group, the R-PV group, the BR-PV group, and the BR-A group, respectively. Overall survival of the BR-PV and BR-A groups was significantly worse than that of the R group and R-PV groups (P < 0.05), although there was no significant difference in overall survival between the R group and the R-PV group (P = 0.310). Multivariate analysis revealed that PV/SMV contact of >180° (P = 0.008) and arterial contact (P < 0.001) were independent prognostic factors of overall survival. CONCLUSION: From the viewpoint of overall survival, the NCCN definition of preoperative resectability status was valid.

A Phase I Study of S-1 and Gemcitabine with Concurrent Radiotherapy in Patients with Non-Metastatic Advanced Pancreatic Cancer.

BACKGROUND/AIMS: To determine the recommended dose (RD) for full-dose S-1 and low-dose gemcitabine combined with radiotherapy in patients with non-metastatic advanced pancreatic cancer. METHODOLOGY: Adult patients with non-metastatic advanced pancreatic cancer (Union for International Cancer Control T stage 3 or 4) were eligible. The weekly intravenous gemcitabine (level 0-1: 200 mg/ml,level 2: 300 mg/m on Days 1, 8, 15, 22, 29, 36) dose was escalated starting from level 1 in a 3+3 design along with full dose twice-daily oral S-1 (level 0: 60 mg/m2/day, level 1-2: 80 mg/ml/day), and was administered on the same days as radiotherapy (1.8 Gy x 28 days). RESULTS: Eight patients were included in this study. A dose-limiting toxicity (DLT) (grade 4 neutropenia) was observed in one of the first three patients in level 1, and three additional patients received the level 1 dose without any severe adverse events. DLTs (grade 3/4 neutropenia) were then observed in the first two patients given level 2 dose. Therefore, level 1 was designated as the RD. Common grade 3/4 toxicities included neutropenia (62.5%), anorexia (37.5%), and pneumonitis (12.5%). CONCLUSIONS: The combination of S-1 and gemcitabine with concurrent radiotherapy is a feasible regimen at the level 1 dose.

Totally laparoscopic hepatectomy exposing the vessels around the tumor intended to secure the surgical margin.

Anatomical hepatectomy (AH) is basically not required for metastatic tumors in terms of oncology, but is required for hepatocellular carcinoma [1-5]; however, the surgeon cannot secure the surgical margin by palpation via a laparoscopic approach. Therefore, AH or partial hepatectomy exposing the vessels around the tumor (PHev) is often better for deep-seated or invisible lesions [6, 7] because unexpected exposure of the tumor on the cutting plane can be avoided by creating a cutting plane on the side of exposed vessels. From August 2008 to December 2012, we performed totally laparoscopic AH or PHev for 29 patients (AH in 21 patients and PHev in 8 patients) to secure the surgical margin of metastatic tumors [8, 9]. The median operative time was 329 (range 147-519) min, with median blood loss of 141 (range 5-430) g. Conversion was performed for one patient whose stump of the Glissonean branch was positive in a frozen section. Additional hepatectomy was performed via an open approach. Postoperative morbidity rate was 20.7 % (peroneal palsy in two patients, ileus in one patient, biloma in one patient, and pulmonary embolism in one patient). Mortality was zero. The median length of hospital stay after surgery was 9 (range 4-21) days. Only one patient, who underwent extended posterior sectorectomy for a 4.2-cm tumor developing close to the right main Glissonean pedicle, had a microscopically positive margin, because the tumors were exposed on the cutting plane. The embedded video demonstrates hepatectomy of the dorsal half-segment of the right anterior sector, during which the liver was divided at the anterior fissure [10] and the border between the anterior and posterior sector. Totally laparoscopic hepatectomy exposing the vessels around the tumor can be performed safely and is useful to secure the surgical margin in patients with a metastatic tumor.

Intraductal papillary mucinous neoplasm of the pancreas and IgG4-related disease: a coincidental association.

BACKGROUND/AIMS: Coexistence of autoimmune pancreatitis (AIP) and pancreatic cancer, elevation of serum IgG4 levels in pancreatic cancer patients, and infiltration of IgG4-positive plasma cells in peritumorous pancreatitis have been described in a few reports. This study examined the relationship between intraductal papillary mucinous neoplasm (IPMN) of the pancreas and peritumorous IgG4-positive lymphoplasmacytic infiltrates. METHODS: Serum IgG4 levels were measured in 54 patients with IPMN (median 70 years, 26 males and 28 females; 13 main duct type and 41 branch duct type). Histological findings focusing on dense lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis were reviewed, and immunostaining with IgG4 and IgG was performed in 23 surgically resected IPMN cases (18 main duct type and 5 branch duct type). The presence of IgG4-positive plasma cells >10/hpf and an IgG4-positive/IgG-positive plasma cell ratio >40% were considered significant. RESULTS: Serum IgG4 levels were elevated in 2 (4%) IPMN patients. Significant infiltration of IgG4-positive plasma cells was detected in 4 IPMN cases (17%). The IgG4-positive/IgG-positive plasma cell ratio was >40% in all 4 cases. In one case with a markedly elevated serum IgG4 level (624 mg/dL), typical lymphoplasmacytic sclerosing pancreatitis (AIP type 1) lesions surrounded the whole IPMN. In the 3 other cases, infiltration of IgG4-positive plasma cells with fibrosis was focally detected mainly in the periductal area around the IPMN. CONCLUSIONS: In a few patients with IPMNs, IgG4-positive plasma cell infiltration can occur in the peritumorous area. The association of an IPMN with AIP type 1-like changes seems to be exceptional and coincidental.

Pancreaticoduodenectomy in portal annular pancreas: report of a case.

Portal annular pancreas (PAP) is a rare anatomical anomaly in which the pancreatic parenchyma surrounds the superior mesenteric vein and portal vein (PV) annularly. This anomaly requires careful consideration in pancreatic resection. A case is presented and the technical issues are discussed. A 61-year-old female was referred to the hospital for suspected papilla Vater adenocarcinoma. Preoperative computed tomography showed that the PV was annularly surrounded by pancreatic parenchyma. Surgery revealed the uncinate process extended extensively behind the PV and fused with the pancreatic body. The pancreas was first divided above the PV, and it was divided again in the body after liberating the PV from pancreatic annulation. The postoperative course was uneventful without pancreatic fistula. It is safer to divide the pancreatic body on the left of the fusion between the uncinate process and the pancreatic body to reduce the risk of pancreatic fistula in pancreaticoduodenectomy for PAP.