Long-term outcome of regional cooperation pathway after endoscopic submucosal dissection for early detection of new gastric cancer.

OBJECTIVES: The Cancer Control Act requires the maintenance of regional cooperation pathways (RCP) for cancer treatment. In 2008, we started RCP for early detection of new gastric cancer after endoscopic submucosal dissection (ESD). In gastric cancer treatment, RCP after surgical resection had been widely used, but little is known about RCP after ESD. This study aimed to evaluate the effectiveness of RCP after ESD. METHODS: This study included 465 patients on whom our RCP was implemented from 2008 to 2018. A regional family physician performed surveillance endoscopy at 3 months and 1 year after ESD and annually thereafter. We retrospectively evaluated the cumulative incidence and treatment outcomes of new gastric cancer and compared them with previous reports. RESULTS: During a median follow-up period of 70.5 months (3-120 months), 58 patients developed new gastric cancers, and metachronous gastric cancer was detected in 55 patients more than 1 year after ESD. The 5-year cumulative incidence rate was 9.8%. Three patients did not want treatment. Among the remaining 55 patients, the initial treatment was ESD in 51 and surgical resection in 4. Eventually, 50 patients (48 in the ESD group and 2 in the surgical resection group) fulfilled the pathologic criteria for curative ESD. There were no deaths due to gastric cancer. CONCLUSION: Our study was the first to reveal the incidence of new gastric cancer after ESD using RCP. Most lesions were cured with ESD, and no patients died of gastric cancer. Therefore, we consider RCPs to be an option for surveillance after ESD.

The clinical management of peripancreatic fluid collection after distal pancreatectomy.

PURPOSE: Peripancreatic fluid collection (PFC) is a frequent radiological finding on postoperative computed tomography (CT) after distal pancreatectomy (DP). We evaluated the risk factors for drainage of PFC after DP to clarify the optimal management of PFC. METHODS: This study included 85 patients who underwent elective DP between January 2010 and December 2020. PFC was defined as an area of fluid located at the pancreatic resection margin on postoperative routine CT on approximately postoperative day 7 (first CT). We retrospectively investigated the relationship between clinical variables, including CT findings and PFC drainage. RESULTS: Drainage was performed in 19 patients (22.4%). Drainage for PFC was significantly associated with a longer postoperative hospital stay, higher PFC volume, presence of air bubbles, and higher white blood cell (WBC) count at the time of the first CT. According to the multivariate analyses, a PFC volume ≥ 60 mL and WBC count ≥ 12,400/µL on the day of the first CT were independent risk factors for PFC drainage after DP. The combination of these 2 factors showed 73.7% sensitivity and 90.9% specificity. CONCLUSION: The PFC volume and WBC count at the first CT were significantly associated with PFC drainage and may help determine the appropriate treatment.

Intracystic papillary neoplasm of the gallbladder concomitant with xanthogranulomatous cholecystitis: a case report.

BACKGROUND: The intracystic papillary neoplasm (ICPN) is a newly established disease concept. It has been regarded as a preinvasive neoplastic lesion, similar to intraductal papillary mucinous neoplasm of the pancreas. Limited information is available on the clinical and imaging features of ICPN. CASE PRESENTATION: A 65-year-old woman was referred to our hospital for assessment of a gallbladder tumor. Contrast-enhanced computed tomography showed a papillary tumor in the fundus of the gallbladder with irregular thickening of the gallbladder wall that spread into the cystic duct. The boundary between the tumor and liver was unclear. The patient was diagnosed with gallbladder cancer with liver invasion. We performed extended cholecystectomy with liver bed resection after confirming the absence of cancer cells in the resection margin of the cystic duct. After pathological examination, the tumor was diagnosed as an ICPN with xanthogranulomatous cholecystitis. The patient was discharged on postoperative day 8 with no complications. CONCLUSIONS: We have described a rare case of ICPN concomitant with xanthogranulomatous cholecystitis. Clinicians should include ICPN as a differential diagnosis in patients with a papillary or polypoid tumor in the gallbladder.

How to Perform Curative Laparoscopic Hepatectomy for Intraoperatively Unidentified Hepatocellular Carcinoma.

BACKGROUND/AIM: Detection of hepatocellular carcinoma using intraoperative ultrasonography (IOUS) is indispensable for successful laparoscopic hepatectomy (LH). This study was performed to evaluate patients with intraoperatively unidentified tumours undergoing LH. PATIENTS AND METHODS: Seven patients who underwent LH for hepatocellular carcinoma and whose tumours were not detected using IOUS were included in this study. Clinical features, preoperative imaging, intraoperative imaging, surgical procedures, and pathological findings were evaluated. RESULTS: Using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging, all the tumours were enhanced in the arterial phase and rapidly washed out, becoming hypointense to the remainder of the liver. All tumours except one were <2 cm in size. Severe liver fibrosis was observed in all cases. Tumours that were invisible on preoperative ultrasonography also could not be detected using IOUS or indocyanine green fluorescence imaging. Five patients underwent hepatectomy based on anatomical landmarks and achieved curative resection, whereas curative resection failed in two patients. CONCLUSION: When tumours cannot be identified by IOUS, LH based on anatomical landmarks should be preferred. Importantly, invisible tumours on preoperative ultrasonography may not be identified intraoperatively during LH.

Efficacy of a half-grip technique using a fine tip LigaSure™, Dolphin Tip Sealer/Divider, on liver dissection in swine model.

BACKGROUND: Recently, a lot of energy devices in the surgical field, especially in the liver surgery, have been developed, and a fine tip LigaSure™, Dolphin Tip Sealer/Divider (DT-SD) also has been used frequently to dissect liver parenchyma as well as ultrasonically activated device (USAD). However, the utility of this instrument for liver dissection (LD) is still unknown. Moreover, to reduce bleeding during LD, a half-grip technique (HGT) was contrived. We herein report an experimental study in swine model to evaluate the feasibility and effectiveness of HGT using DT-SD for LD. METHODS: The swine model experiment was carried out under general anesthesia by veterinarians. LD was performed repeatedly by DT-SD with the HGT (Group A, n = 6), or the conventional clamp-crush technique (CCT) (Group B, n = 6), and by variable mode USAD (Group C, n = 6). The dissection length and depth (cm) as well as bleeding volume (g) were measured carefully, and the dissection area (cm(2)) and speed (cm(2)/min) were calculated precisely. Histological examinations of the dissection surfaces were also executed. Mann-Whitney's U test was used for Statistical analyses with variance at a significance level of 0.05. RESULTS: Among the three groups, the three averages of dissection lengths were unexpectedly equalized to 8.3 cm. The dissection area (cm(2)) was 9.9 ± 5.1 in Group A, 9.8 ± 4.7 in Group B, and 9.9 ± 4.5 in Group C. The mean blood loss during LD was 10.6 ± 14.8 g in Group A, 41.4 ± 39.2 g in Group B, and 34.3 ± 39.2 g in Group C. For Group A, the bleeding rate was the least, 0.9 ± 1.0 g/cm(2), and the average depth of coagulation was the thickest, 1.47 ± 0.29 mm, among the three groups (p < 0.05). The dissection speed in Group A (1.3 ± 0.3 cm(2)/min) was slower, than that in Group C (p < 0.05). CONCLUSIONS: This report indicates firstly that the HGT using DT-SD bring the least blood loss when compared with CCT or USAD. Although the HGT is feasible and useful for LD, to popularize the HGT, further clinical studies will be needed.

Multicenter comparative study of laparoscopic and open distal pancreatectomy using propensity score-matching.

BACKGROUND: Laparoscopic distal pancreatectomy has been shown to be associated with favorable postoperative outcomes using meta-analysis. However, there have been no randomized controlled studies yet. This study aimed to compare laparoscopic and open distal pancreatectomy using propensity score-matching. METHODS: We retrospectively collected perioperative data of 2,266 patients who underwent distal pancreatectomy in 69 institutes from 2006-2013 in Japan. Among them, 2,010 patients were enrolled in this study and divided into two groups, laparoscopic distal pancreatectomy and open distal pancreatectomy. Perioperative outcomes were compared between the groups using unmatched and propensity matched analysis. RESULTS: After propensity score-matching, laparoscopic distal pancreatectomy was associated with favorable perioperative outcomes compared with open distal pancreatectomy, including higher rate of preservation of spleen and splenic vessels (P < 0.001); lower rates of intraoperative transfusion (P = 0.020), clinical grade of pancreatic fistula (International Study Group on Pancreatic Fistula grade B and C; P < 0.001), and morbidity (P < 0.001); and shorter hospital stay (P = 0.001), but a longer operative time (P < 0.001). CONCLUSIONS: Laparoscopic distal pancreatectomy was associated with more favorable perioperative outcomes than open distal pancreatectomy.

Treatment with chemotherapy and dendritic cells pulsed with multiple Wilms' tumor 1 (WT1)-specific MHC class I/II-restricted epitopes for pancreatic cancer.

PURPOSE: We performed a phase I trial to investigate the safety, clinical responses, and Wilms' tumor 1 (WT1)-specific immune responses following treatment with dendritic cells (DC) pulsed with a mixture of three types of WT1 peptides, including both MHC class I and II-restricted epitopes, in combination with chemotherapy. EXPERIMENTAL DESIGN: Ten stage IV patients with pancreatic ductal adenocarcinoma (PDA) and 1 patient with intrahepatic cholangiocarcinoma (ICC) who were HLA-positive for A*02:01, A*02:06, A*24:02, DRB1*04:05, DRB1*08:03, DRB1*15:01, DRB1*15:02, DPB1*05:01, or DPB1*09:01 were enrolled. The patients received one course of gemcitabine followed by biweekly intradermal vaccinations with mature DCs pulsed with MHC class I (DC/WT1-I; 2 PDA and 1 ICC), II (DC/WT1-II; 1 PDA), or I/II-restricted WT1 peptides (DC/WT1-I/II; 7 PDA), and gemcitabine. RESULTS: The combination therapy was well tolerated. WT1-specific IFNγ-producing CD4(+) T cells were significantly increased following treatment with DC/WT1-I/II. WT1 peptide-specific delayed-type hypersensitivity (DTH) was detected in 4 of the 7 patients with PDA vaccinated with DC/WT1-I/II and in 0 of the 3 patients with PDA vaccinated with DC/WT1-I or DC/WT1-II. The WT1-specific DTH-positive patients showed significantly improved overall survival (OS) and progression-free survival (PFS) compared with the negative control patients. In particular, all 3 patients with PDA with strong DTH reactions had a median OS of 717 days. CONCLUSIONS: The activation of WT1-specific immune responses by DC/WT1-I/II combined with chemotherapy may be associated with disease stability in advanced pancreatic cancer.

Wilms tumor gene (WT1) peptide-based cancer vaccine combined with gemcitabine for patients with advanced pancreatic cancer.

Wilms tumor gene (WT1) protein is an attractive target for cancer immunotherapy. We aimed to investigate the feasibility of a combination therapy consisting of gemcitabine and WT1 peptide-based vaccine for patients with advanced pancreatic cancer and to make initial assessments of its clinical efficacy and immunologic response. Thirty-two HLA-A*24:02 patients with advanced pancreatic cancer were enrolled. Patients received HLA-A*24:02-restricted, modified 9-mer WT1 peptide (3 mg/body) emulsified with Montanide ISA51 adjuvant (WT1 vaccine) intradermally biweekly and gemcitabine (1000 mg/m) on days 1, 8, and 15 of a 28-day cycle. This combination therapy was well tolerated. The frequencies of grade 3-4 adverse events for this combination therapy were similar to those for gemcitabine alone. Objective response rate was 20.0% (6/30 evaluable patients). Median survival time and 1-year survival rate were 8.1 months and 29%, respectively. The association between longer survival and positive delayed-type hypersensitivity to WT1 peptide was statistically significant, and longer survivors featured a higher frequency of memory-phenotype WT1-specific cytotoxic T lymphocytes both before and after treatment. WT1 vaccine in combination with gemcitabine was well tolerated for patients with advanced pancreatic cancer. Delayed-type hypersensitivity-positivity to WT1 peptide and a higher frequency of memory-phenotype WT1-specific cytotoxic T lymphocytes could be useful prognostic markers for survival in the combination therapy with gemcitabine and WT1 vaccine. Further clinical investigation is warranted to determine the effectiveness of this combination therapy.

Transumbilical single-incision laparoscopic hepatectomy using precoagulation and clipless technique in a patient with combined hepatocellular-cholangiocarcinoma: a case report.

We report our first case of single-incision laparoscopic hepatectomy in a 43-year-old woman with a 30-mm solitary combined hepatocellular-cholangiocarcinoma. A port of single-incision laparoscopic surgery was inserted through the abdominal wall using a 2.5-cm single incision in the umbilical area. To obtain adequate operative view for the tumor in segment 6, a 5-mm flexible endoscope, roticulated instruments, and a miniloop retractor were used. After precoagulation with a 5-mm flexible microwave probe, liver resection was performed using laparoscopic ultrasonic shears, soft-coagulation devices, and a tissue-sealing knife. Subsequently, cholecystectomy was carried out for a gallbladder polyp. The procedure was successfully completed without conversion to conventional laparoscopic technique. The operation time was 180 minutes and operative blood loss was uncountable. Transumbilical single-incision laparoscopic hepatectomy using precoagulation and clipless techniques is feasible and seems to provide better cosmetic appearance in selected cases by qualified endoscopic liver surgeons.

Impact of chemotherapy with S-1 and oxaliplatin (SOX) in combination with molecular-targeting agents on colorectal liver metastases.

AIM: The aim of this study was to evaluate the impact of chemotherapy with molecular-targeting agents on liver metastases from colorectal cancer. PATIENTS AND METHODS: Six patients with synchronous colorectal liver metastases who underwent hepatectomy after chemotherapy with S-1 and oxaliplatin (SOX) between January 2010 and December 2011 at the Department of Surgery, Kashiwa Hospital, the Jikei University School of Medicine were enrolled. Two patients received only SOX as chemotherapy, while the others received SOX in combination with one of the three molecular-targeting agents, bevacizumab, cetuximab, and panitumumab. RESULTS: In the two patients who received SOX alone, liver metastases completely disappeared at more than six months after starting chemotherapy as shown by computed tomographic (CT) scan. However, malignant cells were diffusely detected by pathological examination at the site of liver metastases, as detected by CT scan before chemotherapy. In the other four patients who received SOX in combination with molecular targets, the size of liver metastases appeared unchanged at three months after limited chemotherapy by CT scan. Pathologically, few malignant cells were detected, only at the borderline of the tumor, while most tumor cells inside the tumor were necrotized and been replaced by fibroconnective tissue. CONCLUSION: Molecular-targeting agents may induce tumor necrosis rapidly from inside the tumor, which might not be detected by CT scan before surgery.

Feasibility study of oxaliplatin with oral S-1 or capecitabine as first-line therapy for patients with metastases from colorectal cancer.

BACKGROUND/AIM: The aim of this study was to determine the feasibility of S-1 plus oxaliplatin (SOX) or capecitabine plus oxaliplatin (XELOX) as first-line therapy for patients with initially unresectable metastases from colorectal cancer. PATIENTS AND METHODS: Fourteen patients with colorectal cancer who underwent elective colorectal resection between January 2009 and December 2010 at the Department of Surgery, Kashiwa Hospital, the Jikei University School of Medicine, with initially unresectable metastatic lesions were enrolled in this study. After curative resection for the primary colorectal cancer, they underwent adjuvant chemotherapy with SOX or XELOX, starting at one month after surgery. RESULTS: Seven patients (50%) received SOX, and the others received XELOX as first-line therapy for initially unresectable metastases from colorectal cancer. Four (29%) patients had complete response for liver metastases over six months after chemotherapy, and liver metastases were subsequently judged to be completely resected by surgery. For the other ten patients, the median progression-free survival was 9.1 months and median overall survival was 24.1 months. There were no patients with grade 3 or 4 adverse reactions throughout the entire chemotherapy. CONCLUSION: Oxaliplatin with oral S-1 or capecitabine as first-line therapy for patients with initially unresectable metastases from colorectal cancer is safe and feasible.

Normalization of serum p53 antibody levels in patients after curative resection for colorectal cancer.

BACKGROUND: The aim of this study was to evaluate the significance of high serum p53 antibody (p53Ab) levels in relation to curative resection of colorectal cancer. PATIENTS AND METHODS: Between 2007 and 2010, 24 patients with colorectal cancer with higher-than-normal preoperative serum p53Ab, measured by enzyme-linked immunosorbent assay, were enrolled in this study. After curative resection, their serum p53Ab and carcinoembryonic antigen (CEA) levels were measured at one, six, 12, 18, and 24 months after surgery. The relationship between clinicopathological features and the presence of serum p53Ab was evaluated. RESULTS: None of the patients developed recurrence up to 24 months after the surgery. The positive rate for CEA was 33.3% before surgery, 16.7% at one month after surgery, and 0% at six months and more, while the rate for p53Ab was 75% at six months, 70.8% at 12 months, 58.3% at 18 months, and 54.2% at 24 months after surgery. The positive rate for serum p53Ab at 24 months after the surgery correlated with the one before and that at one month after the surgery. CONCLUSION: For patients with colorectal cancer and high preoperative serum p53Ab levels, serum p53Ab does not seem to be a useful marker of recurrence after curative resection, since normalization of serum p53Ab levels requires years after surgery.

Usefulness of circulating tumor cells after preliminary chemotherapy for prediction of response to further anticancer therapy in patients with initially unresectable metastatic colorectal cancer.

BACKGROUND/AIM: The aim of this study was to evaluate the usefulness of circulating tumor cells (CTCs) after preliminary chemotherapy for prediction of response to further anticancer therapy in patients with initially unresectable metastatic colorectal cancer. PATIENTS AND METHODS: CTCs from 14 consecutive patients with Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type colorectal cancer with synchronous or metachronous unresectable metastatic lesions were measured using the CellSearch system between January 2009 and December 2011. CTCs were measured before and after chemotherapy. The regimen consisted of four courses (three months) of oxaliplatin with oral S-1 (SOX) + panitumumab. RESULTS: Ten (71%) out of all patients had no detectable CTCs after chemotherapy. Eight out of these ten patients received further chemotherapy, and liver metastases were completely resected in the other two patients; none of these patients died of cancer within a year after starting chemotherapy. The remaining four patients with CTCs continued to have CTCs after chemotherapy, and all four of these patients died of cancer within eight months after starting chemotherapy. The prognosis of the patients who had no detectable CTCs after the chemotherapy was significantly better than that of those who had CTCs even after the chemotherapy (p<0.01). CONCLUSION: CTCs after preliminary chemotherapy may be useful in predicting the response to further anticancer therapy.

Successful adjuvant bi-weekly gemcitabine chemotherapy for pancreatic cancer without impairing patients' quality of life.

BACKGROUND: Although adjuvant gemcitabine (GEM) chemotherapy for pancreatic cancer is standard, the quality of life (QOL) in those patients is still impaired by the standard regimen of GEM. Therefore, we studied whether mild dose-intensity adjuvant chemotherapy with bi-weekly GEM administration could provide a survival benefit with acceptable QOL to the patients with pancreatic cancer. METHODS: After a phase I trial, an adjuvant bi-weekly 1,000 mg/m2 of GEM chemotherapy was performed in 58 patients with pancreatic cancer for at least 12 courses (Group A). In contrast, 36 patients who declined the adjuvant bi-weekly GEM chemotherapy underwent traditional adjuvant 5FU-based chemotherapy (Group B). Careful periodical follow-ups for side effects of GEM and disease recurrence, and assessment of patients' QOL using the EORTC QOL questionnaire (QLQ-C30) and pancreatic cancer-specific supplemental module (QLQ-PAN26) were performed. Retrospectively, the degree of side effects, patients' QOL, compliance rate, disease-free survival (DFS), and overall survival (OS) in Group A were compared with those in Group B. RESULTS: No severe side effects (higher than Grade 2 according to the common toxicity criteria of ECOG) were observed, except for patients in Group B, who were switched to the standard GEM chemotherapy. Patients' QOL was better in Group A than B (fatigue: 48.9 ± 32.1 versus 68.1 ± 36.3, nausea and vomiting: 26.8 ± 20.4 versus 53.7 ± 32.6, diarrhea: 21.0 ± 22.6 versus 53.9 ± 38.5, difficulty gaining weight: 49.5 ± 34.4 versus 67.7 ± 40.5, P < 0.05). Compliance rates in Groups A and B were 93% and 47%. There was a significant difference in the median DFS between both groups (Group A : B =12.5 : 6.6 months, P < 0.001). The median OS of Group A was prolonged markedly compared with Group B (20.2 versus 11.9 months, P < 0.005). For OS between both groups, univariate analysis revealed no statistical difference in 69-year-old or under females, and T1-2 factors, moreover, multivariate analysis indicated three factors, such as bi-weekly adjuvant GEM chemotherapy, T2 or less, and R0. CONCLUSIONS: Adjuvant chemotherapy with bi-weekly GEM offered not only the advantage of survival benefits but the excellent compliance with acceptable QOL for postoperative pancreatic cancer patients.

Possibility of sandwiched liver surgery with molecular targeting drugs, cetuximab and bevacizumab on colon cancer liver metastases: a case report.

A 31-year-old man with sigmoid colon cancer with concomitant simultaneous multiple liver metastases had received FOLFIRI (leucovorin, fluorouracil and irinotecan) and FOLFOX6 (leucovorin, fluorouracil and oxaliplatin) after an ordinary sigmoidectomy. However, his serum carcinoembryonic antigen (CEA) level increased rapidly during the fifteen months after the operation while he was on FOLFOX6. Abdominal computed tomography revealed expanding multiple liver tumors. As the third line chemotherapy, a combination therapy of cetuximab with irinotecan was given, which markedly reduced his levels of serum CEA, and the size and number of liver tumors. He underwent lateral segmentectomy of the liver and microwave coagulation of the liver metastases in the remnant liver. Thereafter, a good quality of life with tumor dormancy was obtained for 6 months. However, his serum CEA started to rise again in the absence of liver tumors. Therefore, FOLFOX6 with bevacizumab was chosen as the fourth line chemotherapy, and the serum CEA was reduced with tumor dormancy. A good quality of life was obtained again at 3 years after the first surgery. This report indicates the effectiveness of sandwiched liver surgery with the molecular targeting drugs cetuximab and bevacizumab on multiple liver metastases of colon cancer, and suggests the possibility of a regimen consisting of bevacizumab following cetuximab.

Determination of circulating tumor cells for prediction of recurrent colorectal cancer progression.

BACKGROUND/AIMS: The aim of this study is to determine the relationship between circulating tumor cells (CTCs) and response to chemotherapy in patients with unresectable metastatic colorectal cancer. METHODOLOGY: CTCs of twelve consecutive patients with K-ras wild type colorectal cancer with synchronous and/or metachronous unresectable metastatic lesions were measured by the cell search system between January 2009 and December 2010. CTCs were measured before and after chemotherapy. The regimen consisted of four courses (three months) of SOX (TS-1+L-OHP) + panitumumab. RESULTS: Four patients (33%) had no detectable CTCs before chemotherapy. For these patients, no CTCs were detected after chemotherapy and their serum carcinoembryonic antigen (CEA) levels decreased after chemotherapy. Four of the other eight patients with positive CTCs had no detectable CTCs after chemotherapy and their serum CEA levels decreased after chemotherapy. The other four of eight patients with positive CTCs continued to have CTCs after chemotherapy and all four patients died of cancer within eight months after starting chemotherapy. On the other hand, all eight patients without CTCs after chemotherapy were alive over a year after starting chemotherapy. CONCLUSIONS: CTCs may be able to predict the response to chemotherapy in patients with unresectable metastatic colorectal cancer.

Is modified Devine exclusion necessary for gastrojejunostomy in patients with unresectable pancreatobiliary cancer?

PURPOSE: Gastrojejunostomy is often performed as palliative surgery for unresectable pancreatobiliary cancer. Modified Devine exclusion (MDE) is a technical variation of gastrojejunostomy, which partially separates the mid-portion of the stomach. We conducted this study to assess whether MDE is necessary for gastrojejunostomy in patients with unresectable pancreatobiliary cancer. METHODS: We compared the postoperative results of MDE (n = 26) with those of conventional gastrojejunostomy (CGJ; n = 20) performed palliatively for unresectable pancreatobiliary cancers. RESULTS: The morbidity rates were 38% after MDE and 50% after CGJ, with 23% and 40% of patients suffering delayed gastric emptying, respectively. Two of the CGJ group patients could never eat again. Modified Devine exclusion slowed the progression of anemia in all of the patients with duodenal bleeding. CONCLUSION: Modified Devine exclusion may be effective for patients with unresectable pancreatobiliary cancer.

Synergistic induction of antigen-specific CTL by fusions of TLR-stimulated dendritic cells and heat-stressed tumor cells.

Dendritic cell (DC)/tumor cell fusion cells (FCs) can induce potent CTL responses. The therapeutic efficacy of a vaccine requires the improved immunogenicity of both DCs and tumor cells. The DCs stimulated with the TLR agonist penicillin-killed Streptococcus pyogenes (OK-432; OK-DCs) showed higher expression levels of MHC class I and II, CD80, CD86, CD83, IL-12, and heat shock proteins (HSPs) than did immature DCs. Moreover, heat-treated autologous tumor cells displayed a characteristic phenotype with increased expression of HSPs, carcinoembryonic Ag (CEA), MUC1, and MHC class I (HLA-A2 and/or A24). In this study, we have created four types of FC preparation by alternating fusion cell partners: 1) immature DCs fused with unheated tumor cells; 2) immature DCs fused with heat-treated tumor cells; 3) OK-DCs fused with unheated tumor cells; and 4) OK-DCs fused with heat-treated tumor cells. Although OK-DCs fused with unheated tumor cells efficiently enhanced CTL induction, OK-DCs fused with heat-treated tumor cells were most active, as demonstrated by: 1) up-regulation of multiple HSPs, MHC class I and II, CEA, CD80, CD86, CD83, and IL-12; 2) activation of CD4+ and CD8+ T cells able to produce IFN- gamma at higher levels; 3) efficient induction of CTL activity specific for CEA or MUC1 or both against autologous tumor; and 4) superior abilities to induce CD107+ IFN-gamma+ CD8+ T cells and CD154+ IFN-gamma+ CD4+ T cells. These results strongly suggest that synergism between OK-DCs and heat-treated tumor cells enhances the immunogenicity of FCs and provides a promising means of inducing therapeutic antitumor immunity.

Combination chemotherapy using TS-1, Paclitaxel and cisplatin for multiple lung metastases from AFP-producing gastric cancer: a case report.

A 61-year-old male had undergone distal gastrectomy followed by right hepatectomy for alpha-fetoprotein-producing gastric cancer and liver metastasis. Subsequently, multiple lung metastases were detected by follow-up chest examinations. Despite treatment with TS-1/Irinotecan (CPT-11)/Cisplatin (CDDP) combination therapy, the metastases increased gradually in size and number. Combination therapy with TS-1/Paclitaxel (TXL)/CDDP was effective, as confirmed by marked reduction in tumor size on chest computed tomography. TS-1/TXL/CDDP chemotherapy was administered repeatedly for relapse of lung metastases. The relapse was controlled twice with this chemotherapy regimen, and the patient remains alive at 52 months after gastrectomy without pulmonary symptoms such as hemosputum. Although patients with postoperative lung metastases from AFP-producing gastric cancer have a dismal prognosis, our clinical experience suggests that TS-1/TXL/CDDP combination therapy may be a useful regimen for such conditions.

Systemic inflammatory response syndrome after hand-assisted laparoscopic distal pancreatectomy.

BACKGROUND: Although the clinical benefits of hand-assisted laparoscopic surgery have been shown in several procedures including colorectal resection, splenectomy and gastrectomy, efficacy and invasiveness in pancreatic surgery have not been well investigated. We assessed the clinical benefits and invasiveness of hand-assisted laparoscopic distal pancreatectomy (HALS-DP) in relation to the occurrence of post-operative systemic inflammatory response syndrome (SIRS). METHODS: Subjects comprised 8 patients underwent HALS-DP (with splenectomy, n = 7; without splenectomy, n = 1) for benign or low malignant pancreatic lesions between March 2004 and December 2005. Indications for HALS-DP consisted of mucinous cystadenoma (n = 4), endocrine tumors (n = 2), serous cystadenoma (n = 1) and pancreatic pseudocyst (n = 1). Controls comprised 9 patients who underwent conventional open distal pancreatectomy (Open-DP) for benign or low malignant lesions of the pancreas in the same period. RESULTS: No significant differences were identified between HALS-DP and Open-DP in operation time. However, intra-operative blood loss, CRP on post-operative day (POD) 1 [5.5 mg/dl (1.8-8.1) vs. 9.7 mg/dl (5.9-12.1); p = .006] and POD 3 [8.5 mg/dl (1.7-11.1) vs. 17.7 mg/dl (10.7-21.5); p = .003], occurrence of post-operative SIRS (13% vs. 67%; p < .05, one-sided), duration of SIRS [0 day (0-1) vs. 1 day (0-4); p = .02] and post-operative hospital stay were significantly lower in HALS-DP than in Open-DP. Furthermore, no pancreatic fistula was seen with HALS-DP, as compared to 2 (22%) with Open-DP. CONCLUSION: HALS-DP is safer and less invasive than Open-DP for benign or low malignant pancreatic tumors.