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In the field of regenerative medicine, tremendous numbers of cells are necessary for tissue/organ regeneration. Today automatic cell-culturing system has been developed. The next step is constructing a non-invasive method to monitor the conditions of cells automatically. As an image analysis method, convolutional neural network (CNN), one of the deep learning method, is approaching human recognition level. We constructed and applied the CNN algorithm for automatic cellular differentiation recognition of myogenic C2C12 cell line. Phase-contrast images of cultured C2C12 are prepared as input dataset. In differentiation process from myoblasts to myotubes, cellular morphology changes from round shape to elongated tubular shape due to fusion of the cells. CNN abstract the features of the shape of the cells and classify the cells depending on the culturing days from when differentiation is induced. Changes in cellular shape depending on the number of days of culture (Day 0, Day 3, Day 6) are classified with 91.3% accuracy. Image analysis with CNN has a potential to realize regenerative medicine industry.

Background: Hepatocellular carcinoma (HCC) is the seventh most common cancer and the third leading cause of cancer deaths worldwide. Hepatitis C virus (HCV) infection is a major risk factor for HCC recurrence after curative resection. This study evaluated anti-HCV antibody (Ab) titer as a prognostic indicator of HCC recurrence after curative hepatic resection., Methods: A total of 82 patients with HCC (anti-HCV Ab positive and hepatitis B surface antigen negative) who underwent curative hepatic resection were evaluated. Anti-HCV Ab titers were measured using a third-generation enzyme immunoassay, and patients were divided into high (n = 41) and low (n = 41) titer groups to compare their clinicopathological characteristics and disease-free survival. Univariate and multivariate analyses were conducted to identify risk factors for early or late recurrence., Results: Multivariate analysis showed that anti-HCV Ab titer and vascular invasion were independent prognostic factors of disease-free survival [odds ratio (OR) 1.9, p = 0.03, and OR 1.8, p = 0.04, respectively]. Subgroup analysis identified only vascular invasion as an independent prognostic factor for early recurrences that were considered residual intrahepatic metastases. Subgroup analysis identified anti-HCV Ab titer and fibrosis grade as independent prognostic factors of late recurrences that were considered to be metachronous multicentric liver carcinogenesis (OR 4.8, p = 0.04, and OR 5.2, p = 0.03, respectively)., Discussion: Anti-HCV Ab titer is a predictive factor for HCC recurrence, especially the risk of late recurrence due to multicentric carcinogenesis. Prevention of liver carcinogenesis after hepatic resection for HCC might be appropriate for patients with high anti-HCV Ab titers.

We have analyzed the structures of glycosphingolipids and intracellular free glycans in human cancers. In our previous study, trace amounts of free N-acetylneuraminic acid (Neu5Ac)-containing complex-type N-glycans with a single GlcNAc at each reducing terminus (Gn1 type) was found to accumulate intracellularly in colorectal cancers, but were undetectable in most normal colorectal epithelial cells. Here, we used cancer glycomic analyses to reveal that substantial amounts of free Neu5Ac-containing complex-type N-glycans, almost all of which were α2,6-Neu5Ac-linked, accumulated in the pancreatic cancer cells from three out of five patients, but were undetectable in normal pancreatic cells from all five cases. These molecular species were mostly composed of five kinds of glycans having a sequence Neu5Ac-Gal-GlcNAc-Man-Man-GlcNAc and one with the following sequence Neu5Ac-Gal-GlcNAc-Man-(Man-)Man-GlcNAc. The most abundant glycan was Neu5Acα2-6Galβ1-4GlcNAcβ1-2Manα1-3Manβ1-4GlcNAc, followed by Neu5Acα2-6Galβ1-4GlcNAcβ1-2Manα1-6Manβ1-4GlcNAc. This is the first study to show unequivocal evidence for the occurrence of free Neu5Ac-linked N-glycans in human cancer tissues. Our findings suggest that free Neu5Ac-linked glycans may serve as a useful tumor marker.

Background: Esophagectomy remains the mainstay treatment for clinical T1bN0M0 esophageal cancer because pathologic lymph node metastases in these patients are not negligible. Recently, chemoradiotherapy (CRT), which can preserve the esophagus, has been reported to be a promising therapeutic alternative to esophagectomy. However, to our knowledge, no comparative studies of esophagectomy and CRT have been reported in clinical T1bN0M0 esophageal cancer., Methods: A total of 173 patients with clinical T1bN0M0 squamous cell carcinoma of the thoracic esophagus were enrolled in this study, 102 of whom were treated with radical esophagectomy (S group) and 71 with definitive CRT (CRT group). Treatment results of both groups were retrospectively compared., Results: No statistically significant difference was found in overall survival, but the S group displayed significantly better progression-free survival than the CRT group. Disease recurrence was observed in 12 S group patients and 20 CRT group patients. The incidence of distant recurrence was similar, while local recurrence and lymph node recurrence were significantly more frequent in the CRT group. In the S group, 20 patients had pathologic lymph node metastasis. The progression-free survival of patients with pathologic lymph node metastasis did not differ from those without nodal metastasis. In the CRT group, local recurrence could be controlled by salvage esophagectomy, but treatment results of lymph node recurrence were poor; only 4 of 12 patients with lymph node recurrences were cured., Conclusions: Selection of patients at high risk of pathologic lymph node metastasis is essential when formulating treatment decisions for clinical T1bN0M0 esophageal cancers.

Background: Indocyanine green (ICG) fluorescence imaging is a promising technique for detection of sentinel node (SN) as it avoids unnecessary resection. However, the ICG fluorescence imaging system cannot be used in laparoscopic surgery because of technological difficulties., Methods: A prototype laparoscopic detection system comprising an electron multiplier charge-coupled device (EM-CCD) as the detector and a xenon lamp as the light source was developed. The CCD camera head was attached to the end of a specially designed laparoscope that could transmit ICG fluorescence. The system allows visualization of both color and fluorescence images. Laparoscopic surgery in ten patients with gastric cancer included SN biopsy using ICG dye, ICG fluorescence images using our system, and laparoscopy-assisted gastrectomy (LAG) with lymphadenectomy. SNs were sliced into 2-mm sections for histological examination and imprint cytology., Results: Immediately after intraoperative ICG injection by endoscopy, the laparoscopic ICG fluorescence imaging system allowed easy visualization of the lymphatic vessels draining from the primary gastric tumor toward the lymph nodes and traced the moving injected dye, whereas lymph vessels and nodes were hardly recognized by ICG green color through a standard laparoscope. Surgeons could confirm the removed lymph nodes stained with ICG by fluorescent imaging. SNs were successfully detected in all patients. Three patients had suspicious metastases in the SNs; two patients had lymph node metastases only in the SNs., Conclusions: Our newly developed laparoscopic ICG fluorescence imaging system is promising in the detection of SNs in laparoscopic gastric cancer surgery. The preliminary results suggest an easier and shorter learning curve of dye-guided SN biopsy in laparoscopic gastric surgery.

Background: The detection of intraperitoneal free cancer cells in colorectal cancer (CRC) patients is associated with a poorer prognosis. The aim of this study was to investigate the effects of intraperitoneal chemotherapy (IPC) with mitomycin C (MMC) on preventing peritoneal recurrence in CRC patients with positive peritoneal lavage cytology findings., Methods: A total of 52 CRC patients who had no clinically confirmed peritoneal dissemination and whose status of peritoneal lavage cytology was positive were investigated. Conventional peritoneal lavage cytology was performed. Overall, 31 of the 52 patients (59.6%) were administered IPC with MMC. Before closure of the abdomen, 4 silicon catheters were inserted into peritoneal cavity. After closure, the perfusate (diluting 20 mg MMC with 500 ml saline) was instilled from the catheter, and all catheters were clumped. All catheters were opened 1 h later., Results: The mean follow-up period was 83.1 months. According to univariate analyses of all 52 patients and the subgroup of 36 patients with stage II or III tumors, patients with IPC had a significantly better peritoneal recurrence-free survival and cancer-specific survival than patients who did not receive IPC (P < 0.005). In multivariate analysis, IPC remained an independent prognostic factor for peritoneal recurrence-free survival in all patients., Conclusions: It appears that IPC with MMC is an effective treatment to prevent peritoneal recurrence and prolong the cancer-specific survival in CRC patients without peritoneal dissemination, but who have positive peritoneal lavage cytology. It is necessary to verify the effectiveness of IPC with MMC in a prospective trial.

Background: Although several studies have suggested an association between circulating tumor cells (CTC) and prognosis after esophageal cancer surgery, large-scale studies are lacking. The aim of this study was to prospectively examine the correlation between CTC and outcome in a large number of patients who underwent esophagectomy., Materials and Methods: A cohort of 244 patients with squamous cell carcinoma of the esophagus who underwent curative surgery between 2002 and 2007 were prospectively analyzed for CTC before surgery and after the thoracic procedure. Reverse transcription-polymerase chain reaction for CEA and SCC antigen mRNA was used to detect cancer cells in the peripheral blood. CTC was defined as positive when at least 1 tumor marker mRNA was detected., Results: CTC was positive in 34 patients (13.9%) before surgery and in 41 patients (16.8%) after the thoracic procedure. Multivariate analysis identified tumor depth (hazard ratio [HR], 0.439; 95% confidence interval [95% CI], 0.268-0.722; P = 0.0012), lymph node metastasis (HR, 2.467; 95% CI, 1.436-4.237; P = 0.0011), venous invasion (HR, 1.802; 95% CI, 1.082-3.002; P = 0.0236), and CTC status after the thoracic procedure (HR, 1.647; 95% CI, 1.032-2.629; P = 0.0365) as independent prognostic factors of disease-free survival. The rates of hematogenous (P = 0.0222) and local (P = 0.0464) recurrences were significantly higher in patients with CTC(+) after the thoracic procedure than those with CTC(-) after the thoracic procedure. Responders to neoadjuvant chemotherapy showed less lymphatic invasion and a decreased positive CTC rate after the thoracic procedure than nonresponders., Conclusions: CTC status after the thoracic procedure is a useful predictor for hematogenous and local recurrences in patients with esophageal cancer.

Background: A lateral pelvic lymph node dissection (LPLD) for lower rectal cancer may be beneficial for a limited number of patients. If sentinel node (SN) navigation surgery could be applied to lower rectal cancer, then unnecessary LPLDs could be avoided. The aim of this study was to investigate the feasibility of lateral region SN biopsy by means of indocyanine green (ICG) visualized with a near-infrared camera system (Photodynamic Eye, PDE)., Methods: This study investigated the existence of a lateral region SN in 25 patients with lower rectal cancer. ICG was injected around the tumor, and the lateral pelvic region was observed with PDE., Results: With PDE, the lymph nodes and lymph vessels that received ICG appeared as shining fluorescent spots and streams in the fluorescence image. This allowed the detection of not only tumor-negative SNs but also tumor-positive SNs as shining spots. The lateral SNs were detected in 6 of 6 T1 and T2 diseases and 17 of 19 T3 diseases. The lateral SNs were successfully identified in 23 (92%) of the 25 patients. The mean number of lateral SNs per patients was 2.1. Of the 23 patients, 6 patients underwent LPLD. Of the 3 patients who had a tumor-negative SN, all dissected lateral non-SNs were negative in all 3 cases., Conclusions: We could detect the lateral SNs, not only in T1 and T2 disease, but also in T3 disease. Although this is only a preliminary study, the detection of lateral SNs in lower rectal cancer by means of the ICG fluorescence imaging system is considered to be a promising technique that may be used for determining the indications for performing LPLD.

Background: Pancreatic ductal adenocarcinoma (PDAC) is still one of the most fatal cancers, although its prognosis has improved recently with the introduction of multimodal therapy. To further develop effective treatment for PDAC, establishment of prognostic indicators for patients receiving multimodal therapy is essential., Methods: Sixty-eight patients receiving curative extended resection combined with preoperative chemoradiation and postoperative chemotherapy for primary PDAC were selected. Immunohistochemistry using anti-CD74 antibody on paraffin-embedded tissue samples was performed, and cases were divided into two groups according to the ratio of CD74-positive cells: expression level I, CD74-positive cells <70%; level II, CD74-positive cells >or=70%. The correlation of CD74 expression level with clinicopathological features and overall survival was evaluated., Results: Forty-seven (69.1%) and 21 (30.9%) patients showed level I and II CD74 expression, respectively. Patients with level II CD74 expression showed a higher rate of lymphatic permeation (P = 0.04) and perineural invasion (P = 0.01) compared with those with level I expression. Patients with level I CD74 expression had a significantly better survival rate than those with level II (P = 0.003). Among the patients with pathological tumor-node-metastasis stages I and II, those with level I CD74 expression showed a significantly better prognosis than those with level II (P = 0.006). Multivariate analysis revealed CD74 expression level and vascular permeation of carcinoma as independent prognostic indicators., Conclusions: CD74 expression proved as a useful prognostic indicator for PDAC treated with multimodal therapy.

Background: The effect of obesity on gastrectomy in patients with gastric cancer is controversial. The degree of abdominal fat increases the technical difficulty of abdominal surgery. This study examined the effect of visceral fat on total gastrectomy and risk factors associated with the formation of pancreatic fistula., Methods: Between February 2001 and April 2007, 191 patients with gastric cancer underwent total gastrectomy. The visceral fat area (VFA) was calculated from computed tomography (CT) scans taken at the level of the umbilicus using FatScan Software. Patients were divided into high- (> or =100 cm(2), n = 52) and low-VFA groups (<100 cm(2), n = 139), and also into high- (> or =25 kg/m(2), n = 47) and low-BMI groups (<25 kg/m(2), n = 144)., Results: Blood loss and incidence of pancreatic fistula were significantly higher in the high- than low-VFA group. However, only blood loss was significantly different between the high- and low-BMI groups. VFA, blood loss, and splenectomy were identified as significant risk factors for pancreatic fistula formation on univariate analysis, and multivariate logistic regression analysis of these factors identified VFA (p = 0.0001) and splenectomy (p = 0.0014) as significant predictors of pancreatic fistula., Conclusions: VFA is a better indicator for pancreatic fistula formation after total gastrectomy than is BMI. Lymph node dissection must be performed carefully, especially in patients with visceral fat accumulation during total gastrectomy with splenectomy.

Background: India ink has been commonly used for preoperative colonic tattooing, but various complications have been reported. This study aimed to evaluate the usefulness of indocyanine green (ICG) marking as a replacement for India ink., Methods: This study enrolled 40 patients who between January 2005 and February 2006 underwent laparoscopic or open surgery for colorectal lesions considered difficult to locate intraoperatively. Because one patient had a history of allergy to iodinated contrast material, metal clipping was used instead of ICG to mark the lesion. Endoscopists injected 5 ml of ICG suspension and saline solution adjacent to the lesion at duplicate locations to evaluate the visibility, duration, and adverse effects of the dye. For 39 patients, the date of the preoperative colonoscopy was not set for examination of the appropriate interval between endoscopic marking and the surgical operation., Results: The median interval between ICG marking and surgery was 4 days (range, 1-73 days). All 29 patients who underwent surgery within 8 days after marking had positive green ICG staining at the time of surgery. After 9 days or more, however, positive staining was seen clearly in only two of the remaining 10 patients. The staining tended to grow weaker and fainter over the time course, eventually dissipating. No perioperative adverse reactions to the dye were observed., Conclusion: This study supports the use of ICG as a safe technique that can be identified reliably during operations performed within 8 days after endoscopic injection.

Background: Secure methods for clinical detection of the sentinel node (SN) are in great demand to avoid unnecessary resection. This was a clinical exploration/feasibility study of a novel detection system for SN biopsy using indocyanine green (ICG) fluorescence imaging in gastric cancer surgery., Methods: SN biopsy using ICG dye was performed in three patients who had gastric cancer. ICG fluorescence images were obtained using a detection system comprising a charge-coupled device (CCD) camera with a cut filter as the detector and light emitting diodes (LED) as the light source. The nodes were also examined simultaneously by an infrared (IR) imaging videoscope., Results: Immediately after intraoperative ICG injection, the fluorescence imaging system allowed easy visualization of the lymphatic vessels draining from the primary gastric tumor toward the lymph nodes and tracing of the moving injected dye. Some lymph vessels and nodes were hardly recognized by ICG green color or IR imaging. The ICG fluorescence system also allowed visualization of the lymph node when ICG was injected the day before surgery, similar to the radio-guided method., Conclusions: Detection of SNs in gastric cancer surgery using the ICG fluorescence imaging system is a promising novel technique and may perhaps prove useful for laparoscopic surgery.

Background: The outcome after resection of advanced pancreatic cancers is extremely poor because of the high incidence of the postoperative development of liver metastasis and local recurrence. We performed a combination of chemoradiation and liver perfusion chemotherapy and extended pancreatectomy., Methods: Nineteen patients with T3 pancreatic head cancers were enrolled. A total of 24 Gy in 12 fractions of 10-MV x-rays with a concurrent intravenous infusion of 5-fluorouracil (5-FU; 3 g/12 days) was administered to the pancreatic head area. An extended pancreaticoduodenectomy was performed, and catheters were placed into the gastroduodenal artery and the superior mesenteric vein. During the first 28 postoperative days, 5-FU was continuously infused via the hepatic artery and portal vein (3.5 g/28 days x 2). Finally, 36 Gy in 18 fractions with 5-FU (3 g/6 days) was applied to the pancreatic bed., Results: After preoperative chemoradiation, four patients did not undergo surgical resection because of distant metastases. Fifteen patients underwent pancreaticoduodenectomy, liver perfusion chemotherapy, and postoperative chemoradiation. No patient developed grade 3 toxicity as a result of preoperative chemoradiation, but one patient (7%) developed grade 3 leukopenia during the postoperative treatments. The morbidity rate was 20% (3 of 15 patients), and the mortality rate was 0%. The overall 3-year survival rate was 53%. The 3-year disease-free survival rate was 66% in patients who pathologically responded well (>50%), versus 0% in patients with poor responses (P = .04)., Conclusions: A combination of preoperative and postoperative chemoradiation plus postoperative liver perfusion chemotherapy with an extended pancreatectomy is feasible, and the long-term outcomes are also promising.

Background: Valosin-containing protein (VCP, also known as p97) exhibits antiapoptotic function and metastasis by activation of nuclear factor kappa-B signaling pathway. Our previous study showed that VCP expression level correlated with prognosis of hepatocellular and gastric carcinoma. In the present study, association of VCP expression with lymph node metastasis and prognosis of pancreatic ductal adenocarcinoma (PDAC) was examined., Methods: VCP expression in 83 patients (46 males and 37 females) of ages ranging from 43 to 80 (median, 66) years who had undergone curative surgery for primary PDAC was analyzed by immunohistochemistry, in which staining intensity in tumor cells was categorized as weaker or equal to (low expression) or stronger (high expression) than that in noncancerous ductal tissue., Results: Thirty-two tumors (38.6%) and 51 tumors (61.4%) were classified as low-VCP-expressing and high-VCP-expressing tumors, respectively. VCP expression correlated significantly with lymph node metastasis (P <.01) but not with various clinicopathologic factors, including age, gender, and histologic differentiation. Multivariate analysis revealed VCP expression as an independent prognosticator for both disease-free and overall survival, along with histologic differentiation, T stage of pathologic tumor-node-metastasis (pTNM) classification, and lymph node metastasis. Furthermore, VCP expression was a prognosticator for disease-free and overall survival in each relatively early stage (I or II) and advanced stage (III) group of pTNM classification., Conclusions: Our results indicate the potential usefulness of VCP expression as a marker of metastasis and overall prognosis of PDAC.

Background: For locally advanced and nonresectable cancer of the pancreas, we performed intra-arterial infusion chemotherapy with angiotensin-II (AT-II). In our preliminary report, this treatment resulted in a median of 14 months of survival without objective adverse effects. This study was designed to clarify the prognostic factor in this chemotherapy by using a larger number of cases., Methods: For 32 patients, intra-arterial chemotherapy was performed: 1 or 2 catheters were intraoperatively placed into the pancreas-supplying arteries. The tissue blood flow and its change by AT-II infusion were determined. For intra-arterial chemotherapy, a mixture of methotrexate (50 or 100 mg/m(2)) and AT-II (.4 microg/kg/hour) was repeatedly infused from the catheter, mainly at our outpatient clinic., Results: With our intra-arterial chemotherapy, the median survival period was 13 months. The median survival period was 19 months in patients without coexisting pancreatitis but was only 9 months in those with it (P =.0003). The presence or absence of coexisting fibrosis in the neighboring uninvolved pancreas offered the only prognostic indicator. The blood flow in cancerous tissue was increased during AT-II infusion, and this was characteristic in the patients whose neighboring uninvolved pancreas had normal parenchyma (nonatrophic) or higher blood flow before AT-II infusion., Conclusions: Because the AT-II infusion played a role in shifting the blood flow from the surrounding uninvolved pancreas to the cancer tissues, we can speculate that cancer tissues might have thereby received a higher dose of anticancer drugs if the surrounding uninvolved pancreas had been nonfibrotic and more rich in tissue blood flow.

Background: Endoscopic resection for treatment of early gastric cancer (EGC) is widely performed. Recently, however, surgeons began performing a limited operation for EGC when endoscopic resection was not indicated. This report discusses the surgical technique and the results of the limited operation, which is generally referred to as "segmental resection" (SR)., Methods: Since 1990, a total of 50 patients with intramucosal invasive EGC of the middle stomach underwent SR. The procedure included a limited gastrectomy, limited lymph node dissection, and preservation of the vagal nerve. We examined the surgical risk, postoperative complications, and patient survival rates and compared the results for the SR-treated patients (group A) with results for patients with EGC who underwent subtotal gastrectomy and systemic lymph node dissection (group B)., Results: Blood loss was less in group A (239 +/- 180 ml) than in group B (342 +/- 176 ml) (P < .05). The incidence of postoperative complications was also lower in group A (2.0%) than in group B (14.0%) (P < .05). The incidence of postoperative cholelithiasis was lower in group A (4.0%) than in group B (18.0%) (P < .05). All patients in both groups are alive without recurrence., Conclusions: Compared with distal gastrectomy, SR for EGC of the middle stomach decreased the surgical risk and postoperative complications without increasing the recurrence rate.

Background: Because there are some difficulties with the diagnosis of invasion or the endoscopic resection technique, almost all gastric tumors are resected surgically. Surgeons now are performing a limited operation for early gastric cancer of the upper stomach (EGCUS) without lymph node metastasis. This paper discusses and evaluates the surgical technique and the results of the limited operation for EGCUS., Patients and Methods: Since 1988, a total of 34 patients with EGCUS, diagnosed as intramucosal invasion, have undergone a limited operation--fundectomy--which includes a limited proximal gastrectomy, a limited lymph node dissection, and a procedure preserving the vagal nerve. The surgical risk, postoperative complications, and survival rates of the fundectomy patients (group A) were compared with those of patients undergoing a total gastrectomy for EGCUS (group B)., Results: Blood loss was lower in group A (300+/-193 mL) than in group B (555+/-316 mL) (P <.05). The incidence of postoperative pancreatic fistula also was lower in group A (0%) than in group B (15.0%) (P <.05). All patients in both groups (except one who died of a cerebral infarction) are alive without recurrence., Conclusion: Compared to the results of a total gastrectomy, performance of a limited fundectomy for EGCUS decreased surgical risk and postoperative complications without decreasing the survival rate.

Background: Tumor cells induce endothelial cell retraction before invasion. In pancreatic cancer cells, the factors affecting endothelial cell retraction are not well-understood., Methods: The activities of the endothelial cell retraction in conditioned media (CM) derived from three human pancreatic cancer cell lines, PSN-1, MiaPaca-2, and Capan-1, were measured for the amount of intercellular junctional transport of FITC dextran through an endothelial cell monolayer in a transwell cell culture system., Results: The CM derived from the three pancreatic cancer cells induced endothelial cell retraction. The endothelial cell retraction activity in the CM from PSN-1 cells was significantly higher than those from MiaPaca-2 and Capan-1 cells. The CM from PSN-1 cells enhanced both the adhesion and the invasion of MiaPaca-2 and Capan-1 cells. The factors with endothelial cell retraction activity in the CM from PSN-1 cells were characterized as heat-stable, trypsin-sensitive glycoproteins ranging from 10,000 to 50,000 in molecular weight, and were found both in heparin-bound and unbound fractions., Conclusions: PSN-1 cells produced and secreted at least two factors inducing the endothelial cell retraction. The factors could play an important role in the establishment of invasion and metastasis of PSN-1 cells.

Background: The prognosis after surgical treatment for type 4 gastric cancer, including linitis plastica, remains poor. The most frequent recurrence mode is retroperitoneal involvement. To remove the tumor and microinvasion surrounding the stomach, extended surgery, left upper abdominal exenteration plus the Appleby's method (LUAE + Apl), has been performed for type 4 cancers since 1983., Patients and Methods: A total of 54 patients with type 4 cancer underwent extended surgery (LUAE + Apl) over the past 11 years. In the LUAE + Apl surgical procedure, the whole stomach, pancreas body and tail, spleen, gallbladder, transverse colon, and left adrenal were removed en bloc. The results of this treatment are reported and the most beneficial application of this procedure (group A) is evaluated and compared with findings in similar patients who underwent common surgery between 1973 and 1983 (group B)., Results: As postoperative complications, pancreatic fistula (30%; control 19%), liver dysfunction (15%; 14%), anastomosis failure (6%; 9%), and infection (4%; 1%) were observed (NS). In group A, one patient died of liver dysfunction and another of multiple organ failure due to major pancreatic fistula. In stage III, the 5-year survival rate of group A (40%) was better than that of group B (20%; p < 0.05). In stage IV, the 5-year survival rate of group A (5%; 3% in group B) was not improved., Conclusion: LUAE + Apl improved the survival of patients with scirrhous cancer in stage III, but it was not effective for those in stage IV. To improve the survival of patients in stage IV, a new concept of treatment and supportive therapy needs to be used.

The bitter and related constituents have been isolated fromVernonia amygdalina (Compositae), a plant ingested by wild chimpanzees possibly suffering from parasite-related diseases in the Mahale Mountains National Park, Tanzania. Isolated from the plant were four known sesquiterpene lactones, seven new steroid glucosides, and two aglycones of the glucosides. The sesquiterpene lactones showed significant in vitro antischistosomal, plasmodicidal, and leishmanicidal activities. Antischistosomal activity was also found for the major steroid glucoside, vernonioside B1. A trend in the glucosides to show significant antischistosomal, plasmodicidal, and amebicidal activities when the sugar moiety was removed, was observed. Vernodalin, judged as the most significant constituent for antiparasitic activities in vitro, was tested for in vivo antischistosomal effect. It was, however, highly toxic to the cercaria-infected mouse. Chimpanzees have been only rarely observed to ingest anything but the pith of the young stem. The occurrence of vernonioside B1 and its aglycone vernoniol B1, the major constituents among the steroid-related constituents, were detected at significant levels in the pith. However, vernodalin was abundant only in the leaves and bark. Thus, chimpanzees at Mahale were hypothesized to control parasite-related diseases by ingesting the young pith of this tree containing steroid-related constituents.

The machanisms by which the larvae of the larch sawfly,Pristiphora erichsonii (Hartig), are prevented from feeding on the single needles of the new shoot of tamarack,Larix laricina (DuRoi) K. Koch, were studied. As a result of extensive purification attempts, five deterrent chemicals were isolated and identified. They are: abietic, dehydroabietic, 12-methoxyabietic, sandaracopimaric, and isopimaric acid. These chemicals, particularly the first two, are abundant in mid-July to August in the single needles and, apparently, provide the basis for the deterrency against the larval feeding.