Risk model for severe postoperative complications after total pancreatectomy based on a nationwide clinical database.

BACKGROUND: Total pancreatectomy is required to completely clear tumours that are locally advanced or located in the centre of the pancreas. However, reports describing clinical outcomes after total pancreatectomy are rare. The aim of this retrospective observational study was to assess clinical outcomes following total pancreatectomy using a nationwide registry and to create a risk model for severe postoperative complications. METHODS: Patients who underwent total pancreatectomy from 2013 to 2017, and who were recorded in the Japan Society of Gastroenterological Surgery and Japanese Society of Hepato-Biliary-Pancreatic Surgery database, were included. Severe complications at 30 days were defined as those with a Clavien-Dindo grade III needing reoperation, or grade IV-V. Occurrence of severe complications was modelled using data from patients treated from 2013 to 2016, and the accuracy of the model tested among patients from 2017 using c-statistics and a calibration plot. RESULTS: A total of 2167 patients undergoing total pancreatectomy were included. Postoperative 30-day and in-hospital mortality rates were 1·0 per cent (22 of 2167 patients) and 2·7 per cent (58 of 167) respectively, and severe complications developed in 6·0 per cent (131 of 2167). Factors showing a strong positive association with outcome in this risk model were the ASA performance status grade and combined arterial resection. In the test cohort, the c-statistic of the model was 0·70 (95 per cent c.i. 0·59 to 0·81). CONCLUSION: The risk model may be used to predict severe complications after total pancreatectomy.

ANTECEDENTES: La pancreatectomía total está indicada cuando se requiere la resección completa de tumores localmente avanzados o ubicados en el centro del páncreas. Sin embargo, existen pocos artículos que describan los resultados clínicos después de una pancreatectomía total. El objetivo de este estudio observacional retrospectivo fue evaluar los resultados clínicos después de una pancreatectomía total utilizando un registro nacional y crear un modelo de riesgo de complicaciones postoperatorias graves. MÉTODOS: Se incluyeron aquellos pacientes que se sometieron a una pancreatectomía total entre 2013 y 2017 y que fueron registrados en la base de datos de la Sociedad Japonesa de Cirugía Gastrointestinal y de la Sociedad Japonesa de Cirugía Hepato-Bilio-Pancreática. Las complicaciones graves a los 30 días se definieron como Clavien-Dindo grado III con reintervención o grado IV/V. Se analizó la aparición de complicaciones graves de los pacientes desde 2013 a 2016 y se evaluó la precisión del modelo entre los pacientes operados desde 2017 usando estadísticos c y un gráfico de calibración. RESULTADOS: Se incluyeron 2.167 pacientes sometidos a una pancreatectomía total. La mortalidad postoperatoria a los 30 días y la mortalidad hospitalaria fueron del 1,0% (22/2167) y del 2,7% (58/2167), respectivamente, y las complicaciones graves ocurrieron en el 6,0% (131/2167) de los pacientes. Los factores que mostraron una fuerte asociación positiva con los resultados en este modelo de riesgo fueron el estado funcional según la Sociedad Americana de Anestesiología y la resección arterial combinada. En la cohorte de prueba, el estadístico c del modelo fue de 0,70 (i.c. del 95% 0,59-0,81). CONCLUSIÓN: El modelo de riesgo puede usarse para predecir las complicaciones graves después de una pancreatectomía total.

Randomized clinical trial of landiolol hydrochloride for the prevention of atrial fibrillation and postoperative complications after oesophagectomy for cancer.

BACKGROUND: Atrial fibrillation is common after oesophageal surgery. The aim of this study was to evaluate whether landiolol hydrochloride was effective and safe in the prevention of atrial fibrillation after oesophagectomy, and to see whether a reduction in incidence of atrial fibrillation would reduce other postoperative complications. METHODS: This single-centre study enrolled patients scheduled for transthoracic oesophagectomy in a randomized, double-blind, placebo-controlled trial between March 2013 and January 2016. Enrolled patients were randomized with a 1 : 1 parallel allocation ratio to either landiolol prophylaxis or placebo. The primary endpoint was the occurrence of atrial fibrillation after oesophagectomy. Secondary endpoints were incidence of postoperative complications, and effects on haemodynamic and inflammatory indices. RESULTS: One hundred patients were enrolled, 50 in each group. Postoperative atrial fibrillation occurred in 15 patients (30 per cent) receiving placebo versus five (10 per cent) receiving landiolol (P = 0·012). The overall incidence of postoperative complications was significantly lower in the landiolol group (P = 0·046). In the landiolol group, postoperative heart rate was suppressed effectively, but the decrease in BP was not harmful. The interleukin 6 level was significantly lower on days 3 and 5 after surgery in the landiolol group (P = 0·001 and P = 0·002 respectively). CONCLUSION: Landiolol was effective and safe in preventing atrial fibrillation after oesophagectomy. Registration number: UMIN000010648 (http://www.umin.ac.jp/ctr/).

Phase I/II study of divided-dose docetaxel, cisplatin and fluorouracil for patients with recurrent or metastatic squamous cell carcinoma of the esophagus.

Squamous cell carcinoma of the esophagus (SCCE) has a poor prognosis compared with other gastrointestinal cancers. Many patients present with locoregional unresectable or metastatic disease at the time of diagnosis. For these patients with metastatic esophageal cancer, chemotherapy is generally indicated. The aim of this phase I/II study was to evaluate the efficacy and safety of the combined use of docetaxel, cisplatin (CDDP) and 5-fluorouracil (5-FU)(DCF) in patients with recurrent/metastatic SCCE. This study adopted divided doses of docetaxel and CDDP in order to reduce the toxicities of the treatment. The dose of docetaxel was escalated using the following protocol in the phase I stage: level 1, 30 mg/m2; level 2, 35 mg/m2 and level 3, 40 mg/m2, which was intravenously infused for 2 hours on days 1 and 8. CDDP was administered at a dose of 12 mg/m2 infused for 4 hours on days 1-5. The 5-FU was administered at a dose of 600 mg/m2 continuously infused from day 1 to 5. This regimen was repeated every 4 weeks. The study subjects were nine patients (phase I) and 48 patients (phase II). The recommended dose was determined as level 3 in phase I. In the phase II stage, the overall response rate was 62.5%, with a complete response rate of 12.5%. The median progression-free survival was 6 months, and the median overall survival was 13 months. Grade 3/4 toxicities of leukopenia, neutropenia and febrile neutropenia occurred in 64.6%, 68.8% and 14.6% of the patients, while grade 3/4 non-hematological toxicities were relatively rare. No treatment-related death was recorded. This modified DCF regimen with divided doses can be a tolerable and useful regimen of definitive chemotherapy for unresectable SCCE because of its high efficacy, although adequate care for severe neutropenia must be administered.

Randomized clinical trial comparing long-term quality of life for Billroth I versus Roux-en-Y reconstruction after distal gastrectomy for gastric cancer.

BACKGROUND: Patients' quality of life (QoL) deteriorates remarkably after gastrectomy. Billroth I reconstruction following distal gastrectomy has the physiological advantage of allowing food to pass through the duodenum. It was hypothesized that Billroth I reconstruction would be superior to Roux-en-Y reconstruction in terms of long-term QoL after distal gastrectomy. This study compared two reconstructions in a multicentre prospective randomized clinical trial to identify the optimal reconstruction procedure. METHODS: Between January 2009 and September 2010, patients who underwent gastrectomy for gastric cancer were randomized during surgery to Billroth I or Roux-en-Y reconstruction. The primary endpoint was assessment of QoL using the Functional Assessment of Cancer Therapy - Gastric (FACT-Ga) questionnaire 36 months after surgery. RESULTS: A total of 122 patients were enrolled in the study, 60 to Billroth I and 62 to Roux-en-Y reconstruction. There were no differences between the two groups in terms of postoperative complications or mortality, and no significant differences in FACT-Ga total score (P = 0·496). Symptom scales such as epigastric fullness (heaviness), diarrhoea and fatigue were significantly better in the Billroth I group at 36 months after gastrectomy (heaviness, P = 0·040; diarrhoea, P = 0·046; fatigue, P = 0·029). The rate of weight loss in the third year was lower for patients in the Billroth I group (P = 0·046). CONCLUSION: The choice of anastomotic reconstruction after distal gastrectomy resulted in no difference in long-term QoL in patients with gastric cancer. REGISTRATION NUMBER: NCT01065688 (http://www.clinicaltrials.gov).

Phase II trial of combination therapy of gemcitabine plus anti-angiogenic vaccination of elpamotide in patients with advanced or recurrent biliary tract cancer.

Background Elpamotide is an HLA-A*24:02-restricted epitope peptide of vascular endothelial growth factor receptor 2 (VEGFR-2) and induces cytotoxic T lymphocytes (CTLs) against VEGFR-2/KDR. Given the high expression of VEGFR-2 in biliary tract cancer, combination chemoimmunotherapy with elpamotide and gemcitabine holds promise as a new therapy. Patients and Methods Patients with unresectable advanced or recurrent biliary tract cancer were included in this single-arm phase II trial, with the primary endpoint of overall survival. Survival analysis was performed in comparison with historical control data. The patients concurrently received gemcitabine once a week for 3 weeks (the fourth week was skipped) and elpamotide once a week for 4 weeks. Results Fifty-five patients were registered, of which 54 received the regimen and were included in the full analysis set as well as the safety analysis set. Median survival was 10.1 months, which was longer than the historical control, and the 1-year survival rate was 44.4%. Of these patients, injection site reactions were observed in 64.8%, in whom median survival was significantly longer (14.8 months) compared to those with no injection site reactions (5.7 months). The response rate was 18.5%, and all who responded exhibited injection site reactions. Serious adverse reactions were observed in five patients (9%), and there were no treatment-related deaths. Conclusion Gemcitabine and elpamotide combination therapy was tolerable and had a moderate antitumor effect. For future development of therapies, it will be necessary to optimize the target population for which therapeutic effects could be expected.

Randomized clinical trial of defaecatory function after anterior resection for rectal cancer with high versus low ligation of the inferior mesenteric artery.

BACKGROUND: Defaecatory function is often poor after anterior resection. Denervation of the neorectum following high ligation of the inferior mesenteric artery (IMA) is a possible cause of impaired defaecatory function. The purpose of this randomized clinical trial was to clarify whether the level of ligation of the IMA in patients with rectal cancer affects defaecatory function. METHODS: Between 2008 and 2011, patients who underwent anterior resection for rectal cancer were randomized to receive either high or low ligation of the IMA. The primary endpoint was to demonstrate the superiority of low ligation in terms of defaecatory function. RESULTS: One hundred patients were enrolled in the study; 51 were randomized to high ligation of the IMA and 49 to low ligation. There were no differences between the groups in terms of clinical data, except tumour stage, which was more advanced in the high-ligation group (P = 0·046). Nor were there any differences in defaecatory function, self-assessment of defaecation, Faecal Incontinence Quality of Life scale or continence score between groups at 3 months and 1 year. The number of harvested lymph nodes was similar. The rate of symptomatic anastomotic leakage was 16 per cent in the high-ligation group and 10 per cent in the low-ligation group (P = 0·415). CONCLUSION: The level of ligation of the IMA in patients with rectal cancer did not affect defaecatory function or the incidence of postoperative complications. REGISTRATION NUMBER: NCT00701012 (http://www.clinicaltrials.gov).

Randomized clinical trial of isolated Roux-en-Y versus conventional reconstruction after pancreaticoduodenectomy.

BACKGROUND: Pancreaticoduodenectomy (PD) is associated with a high incidence of postoperative complications including pancreatic fistula. This randomized clinical trial compared the incidence of pancreatic fistula between the isolated Roux-en-Y (IsoRY) and conventional reconstruction (CR) methods. METHODS: Patients admitted for PD between June 2009 and September 2012 in a single centre were assigned randomly to CR or IsoRY. The primary endpoint was the incidence of pancreatic fistula (grade A-C) defined according to the International Study Group on Pancreatic Fistula. Secondary endpoints were complication rates, mortality and hospital stay. Multiple logistic regression analysis was performed to identify factors associated with pancreatic fistula. RESULTS: Some 153 patients were randomized, 76 to CR and 77 to IsoRY; two patients from the IsoRY group were excluded after randomization. Pancreatic fistula occurred in 26 patients (34 per cent) in the CR group and 25 (33 per cent) in the IsoRY group (P = 0·909). The number of patients with a clinically relevant pancreatic fistula (grade B or C) was similar in the two groups (10 and 11 patients respectively; P = 0·789), as were complication rates (42 versus 40 per cent; P = 0·793) and mortality (none in either group; P = 0·999). Soft pancreas was the only independent risk factor for pancreatic fistula (odds ratio 4·42, 95 per cent confidence interval 1·85 to 10·53; P <0·001). CONCLUSION: This study showed that IsoRY reconstruction does not reduce the incidence of pancreatic fistula compared with CR. REGISTRATION NUMBER: NCT00915863 (http://www.clinicaltrials.gov/) and UMIN000001967 (http://www.umin.ac.jp/).

Preoperative evaluation of the extrahepatic bile duct structure for laparoscopic cholecystectomy.

BACKGROUND: The incidence of aberrant bile duct injury associated with laparoscopic cholecystectomy (LC) has not yet been adequately examined. This study aimed to clarify the types of normal cystic ducts and the incidence of aberrant extrahepatic bile ducts, and to search for a method of avoiding injuries during LC. METHODS: Aberrant hepatic ducts were retrospectively categorized into five types according to the pattern of the cystic ducts and the accessory hepatic ducts by preoperative endoscopic retrograde cholangiography or multidetector three-dimensional computed tomography using drip infusion cholangiography. The aberrant bile ducts were classified as type A (merging at the right side of the common bile duct), type B (merging at the anterior side), or type C (merging at the posterior left side). RESULTS: The intrahepatic bile ducts and cystic duct were clearly shown for 1,044 of the 1,278 patients who underwent LC. Secondary branches of aberrant cystic ducts were observed in 37 cases (3.5%), and accessory hepatic ducts were observed in 30 cases (2.9%). A comparison of the difficulties encountered with LC for each type based on the merging patterns of cystic ducts showed that type C needed a much longer operation time for LC than the other types. CONCLUSIONS: A preoperative evaluation of the bile duct tract and the accessory hepatic duct before LC is important. Patients with a cystic duct merging normally into the posterior left side of the common hepatic duct (type C) experienced difficulty when undergoing LC. The authors have safely performed LC with the use of an endoscopic nasobiliary drainage tube in type D cases (cystic duct merging with the right hepatic duct), in type IV cases (cystic duct merging with an accessory hepatic duct).

Gender differences in postoperative pain after laparoscopic cholecystectomy.

BACKGROUND: Some evidence suggests that females have a lower pain threshold and a lower tolerance to painful stimuli. This study investigated gender differences in postoperative pain after laparoscopic cholecystectomy (LC) on the basis of visual analog pain scale (VAS) scores and the clinical course. METHODS: The 100 patients in this study (46 males and 54 females) underwent LC for cholecystolithiasis or gallbladder polyps without intraoperative complications. An 8-mm Penrose drain was retained for 42 h below the liver bed. All the patients were hospitalized for 4 days after LC, and the pain reported by patients, the time course of changes in the highest body temperature, the leukocyte count, and the C-reactive protein level were studied comparatively for the male and female patients. RESULTS: The VAS scores were significantly higher for the female patients than for the male patients at 24 h (62.7 +/- 24.6 vs 47.0 +/- 23.3; p = 0.0015) and at 48 h (39.2 +/- 24.3 vs 28.3 +/- 19.1; p = 0.0137) after LC. The female patients used analgesics more frequently and had significantly higher body temperatures than the male patients on day 1 (37.2 +/- 0.6 vs 36.9 +/- 0.4; p = 0.0037) and day 2 (36.9 +/- 0.6 vs 36.6 +/- 0.4; p = 0.0037) after surgery. CONCLUSIONS: Early postoperative pain after LC was more severe in female patients, and patients with high VAS scores tended to use analgesics more frequently.

Carcinoembryonic antigen-specific suicide gene therapy of cytosine deaminase/5-fluorocytosine enhanced by the cre/loxP system in the orthotopic gastric carcinoma model.

Tumor-specific gene delivery is crucial to achieving successful effects in suicide gene therapy. Carcinoembryonic antigen (CEA) promoter has been widely used for this purpose, but the expression level of tumor-specific promoters such as CEA promoter is generally low. In the previous study, we used the Cre/loxP system and showed that LacZ expression by the CEA promoter was remarkably enhanced and maintained its specificity using the Cre/loxP regulation system. In this study, the Cre/loxP system was first applied to augmentation of selective expression of the cytosine deaminase (CD) gene as a suicide gene therapy in CEA-producing cells. The double infection with AxCEANCre expressing Cre recombinase under the control of the CEA promoter and AxCALNLCD expressing the CD gene under the control of the CAG promoter by the Cre switching system rendered CEA-producing tumor cells 13-fold more sensitive to 5-fluorocytosine (5-FC) compared with the single infection with AxCEACD expressing CD gene driven by the CEA promoter. The therapeutic efficacy of the enhanced CD/5-FC suicide gene therapy was evaluated in orthotopic implantation models of human gastric carcinoma. Adenovirus vectors (1 x 10(9) plaque-forming units) were administered i.p. into mice three times, and then 5-FC was administered i.p. for the next 10 days. Tumor volume and weight in mice treated with AxCEANCre and AxCALNLCD/5-FC were significantly reduced as compared with those in mice treated not only with Mock (AxCALacZ) but also with AxCEACD/5-FC (P < 0.0001). This beneficial effect on tumor burden was also reflected in the overall survival. The survival periods of the mice treated with AxCEANCre and AxCALNLCD/5-FC were longer than those of mice treated with Mock or AxCEACD/5-FC (P < 0.01). These results suggested that application of the Cre/loxP system could provide a new approach for enhanced selective suicide gene therapy of CD/5-FC for the treatment of advanced gastric carcinoma.

Overexpression of pyrimidine nucleoside phosphorylase enhances the sensitivity to 5'-deoxy-5-fluorouridine in tumour cells in vitro and in vivo.

5-Fluorouracil (5-FU) and 5'-deoxy-5-fluorouridine (5'-DFUR), a prodrug of 5-FU, are representative of the chemotherapeutic agents for colorectal adenocarcinomas. Pyrimidine nucleoside phosphorylase (PyNPase) catalyses the conversion of 5'-DFUR to 5-FU, the activated form. Murine adenocarcinoma CT26 cells were transfected with human PyNPase cDNA. The engineered transfectants producing PyNPase augmented the response to 5'-DFUR in vitro and in vivo. Animals were administered by means of intraperitoneal (i.p.) injection, and not orally, in order to obtain a better efficiency of absorption. The tumours of the transfected cells nearly all disappeared, even following treatment with quite a small amount of the anticancer agent. The animals injected with the tranfected cells were protected against subsequent challenge with the parental tumour cell line. These findings demonstrate that PyNPase gene transfection increases the sensitivity to 5'-DFUR, and thereby decreases the toxicity of the agent.

Chemosensitivity testing with highly purified fresh human tumour cells with the MTT colorimetric assay.

A major problem associated with the succinate dehydrogenase inhibition (SDI) test using tetrazolium dye (MTT) as a cancer chemosensitivity testing is the contamination of non-malignant cells in the tumour tissues. Highly purified fresh human tumour cells from 44 solid tumours and 24 malignant ascites were used for the MTT assay. The purity of tumour cells was greater than 90% after separation on Ficoll-Hypaque and Percoll discontinuous gradients. The OD570 obtained from tumour cells alone was higher than that from non-malignant cells. The chemosensitivity of tumour cells was distinct from that of non-malignant cells. Moreover, the chemosensitivity of highly purified tumour cells was also distinct from that of non-purified cells just separated from tumour tissues. 31 of the 68 patients had evaluable lesions, and received cancer chemotherapy according to the results of MTT assay using highly purified tumour cells. A clinical response was obtained in 10 of the 31 patients (response rate = 32.3%, 5 complete responses, 5 partial responses).

Clinical significance of quantitative analysis of carcinoembryonic antigen assessed by flow cytometry in fresh human gastric cancer cells.

The expression of carcinoembryonic antigen(CEA) on tumor cells freshly excised from 51 patients with gastric cancer was studied using flow cytometry. The expression of CEA by flow cytometry was more quantitative than that by immunohistochemical staining. There was no relationship between the fluorescence intensity assessed by flow cytometry and serum CEA levels, except for patients with a high titer of serum CEA. The patients with high grade CEA expression on tumor cells by flow cytometry had poor prognoses, compared to patients with low CEA expression in undifferentiated gastric cancer. Thus, it is suggested that the quantitative CEA expression on tumor cells by flow cytometry could be a useful prognostic marker in postoperative gastric cancer patients.

Synergistic effects of tamoxifen and cepharanthine for circumventing the multidrug resistance.

We examined the synergistic effects of tamoxifen (TAM) and cepharanthine (CEP) for doxorubicin (DOX) sensitivity using MTT assay. The augmentation of DOX sensitivity by TAM and CEP was significantly correlated with the P-glycoprotein expression. The cytotoxic effect of DOX with TAM and CEP was significantly higher than that of DOX alone, or DOX with TAM, and this synergistic effect was dominant in cell lines with high expression of P-glycoprotein. It was also examined that the intracellular concentration of DOX was increased in combined exposure of TAM and CEP, compared with the exposure of TAM, because TAM and CEP promoted the influx and inhibited the efflux of DOX. Thus, TAM and CEP might be able to circumvent DOX-resistance for treatment in cancer patients.

Interleukin-4 inhibits lak and initial phase til activity via interleukin-2 receptor.

In the present study, we analyzed the proliferation and cytotoxic activities of LAK cells and initial phase TILs by stimulation with IL-4. IL-4 obviously inhibited the DNA synthesis of LAK cells and initial phase TILs at the concentration of 250 pg/ml and 25 pg/ml, respectively. Furthermore, IL-4 (25 ng/ml for LAK cells, 25 pg/ml for initial phase TILs) suppressed the cytotoxic activities against K562, KATO-III, and autologous tumor cells. The discrepancy of the concentration between the proliferation and the cytotoxicicity by IL-4 suggested different pathways in terms of the generation of LAK cells. In order to clarify the inhibitory mechanism of IL-4, we measured the expression of IL-2 receptor. IL-2 receptor alpha chain was strongly down-regulated by IL-4. Thus, IL-4 modulates the activation of LAK cells and initial phase TILs via the IL-2 receptor alpha chain.

Enhancement of tumor cell susceptibility to tumor-infiltrating lymphocytes by cisplatin.

Some means of enhancing the susceptibility of tumor cells to tumor-infiltrating lymphocytes (TIL) are required in adoptive immunotherapy. This study was designed to investigate whether or not tumor cell lysis by TIL was enhanced by treatment of the tumor cells with cisplatin, and also to clarify the mechanism of cisplatin's action on tumor cells. Autologous tumor cells and established cancer cell lines, including KATO-III and MKN-28, were used. Cytotoxic activities of TIL, the surface antigens of tumor cells, conjugation of TIL and tumor cells, and the production of TNF alpha from TIL were analyzed. Tumor cells treated with 2 micrograms/ml cisplatin for 12 h in vitro were more susceptible to bulk-cultured TIL and TIL clones. The surface antigens of tumor cells were not altered by the treatment with cisplatin. Cisplatin-treated tumor cells showed a higher binding ratio to TIL than did non-treated tumor cells. The anti-(tumor necrosis factor) (anti-TNF) or anti-TNF receptor antibody blocked the enhancement of cytotoxic activity by cisplatin. Thus, it was clarified that cisplatin enhanced the susceptibility of tumor cells to bulk-cultured TIL and TIL clones. Furthermore, the enhancement of cytotoxic activity by TIL in cisplatin-treated tumor cells was caused by a higher binding ratio to TIL and higher susceptibility to the TNF produced by TIL.

Clinical features and management of hepatic portal venous gas: four case reports and cumulative review of the literature.

HYPOTHESIS: Hepatic portal venous gas (HPVG) has been considered a rare entity associated with a grave prognosis. Since 1978, when Liebman et al reviewed 64 cases of HPVG and reported a mortality of 75%, the number of reported cases has been increasing. DESIGN: Case series. PATIENTS AND METHODS: We reviewed the literature on 182 cases of HPVG in adults, including 4 of our patients, (transplantation and abdominal trauma cases were excluded) and analyzed the cause, pathogenesis, and clinical features. RESULTS: In this series, the underlying clinical events associated with HPVG were bowel necrosis (43%), digestive tract dilatation (12%), intraperitoneal abscess (11%), ulcerative colitis (4%), gastric ulcer (4%), Crohn disease (4%), complications of endoscopic procedures (4%), intraperitoneal tumor (3%), and other (15%). The overall mortality was 39% but varied depending on the underlying disease. CONCLUSIONS: Hepatic portal venous gas is a lethal or curable entity caused by various diseases. The underlying disease associated with HPVG determines the clinical features and prognosis of the patients. The treatment of patients with HPVG should be directed to the underlying disease.

Clinical effects of chemoimmunotherapy for patients with peritoneal carcinomatosis.

The present study was undertaken to determine whether chemoimmunotherapy using activated killer cells is better than chemotherapy alone for cancer patients with peritoneal carcinomatosis. Thirty-one cancer patients received adoptive immunotherapy by activated killer cells and chemotherapy by anticancer drugs selected by a chemosensitivity test (chemoimmunotherapy group), and another 31 cancer patients received chemotherapy (chemotherapy group). The regimen of chemotherapy was determined by the results of a chemosensitivity test in both groups. The clinical effects including response rate and survival were assessed. Five patients (16.1%) achieved complete response (CR), and 17 patients (54.8%) partial response (PR) in the chemoimmunotherapy group (response rate: 22/31 patients = 71.0%), whereas 4 patients (12.9%) achieved CR, and 5 patients (16.1%) PR in the chemotherapy group (response rate: 9/31 patients = 29.0%). The response rate was higher in chemoimmunotherapy group than in chemotherapy group (p<0.05). However, no difference was observed in survival between the two groups. Therefore, it is necessary to develop methods to induce more potent killer cells for adoptive immunotherapy.

Cisplatin modulates tumor cell susceptibility to tumor-infiltrating lymphocytes in vivo.

We investigated the in vivo augmentation of susceptibility of tumor cells to tumor-infiltrating lymphocytes (TILs) with cisplatin (CDDP). TILs showed cytotoxicity against autologous and established tumor cells. Pretreatment of tumor cells with CDDP 2 mu g/ml for 12 h enhanced the susceptibility of tumor cells to TILs in vitro. TILs and autologous tumor cells were obtained from malignant ascites of patients, before and after the intraperitoneal administration of CDDP. TILs had higher cytotoxicity against autologous tumor cells of CDDP treated as compared to untreated control tumor cells, providing direct evidence of in vivo immunomodulatory effect of CDDP in cancer patients.