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OBJECTIVES The prognostic nutritional index (PNI) is an indicator of systemic immune-nutritional condition and is a well-known prognostic biomarker in lung cancer patients. Tumour-infiltrating lymphocytes (TILs) is a specific histological feature of cancers, influencing an individual’s immunological tumour responses. However, whether PNI can reflect lung cancer patients’ prognosis through local immunity such as TIL is unclear. METHODS We selected 64 lung squamous cell carcinoma patients who underwent curative operations. We investigated the significance of preoperative PNI level and evaluated the relationship between PNI and immune cells surrounding the lung cancer tissue using immunohistochemical analysis of a cluster of differentiation (CD)3, CD4, CD8 and CD68. RESULTS A low-PNI level was significantly associated with a worse postoperative prognosis (P = 0.042). The PNI (hazard ratio 2.768, 95% confidence interval 1.320–5.957; P = 0.007) was an independent prognostic factor. The low-PNI group had a significantly shorter recurrence-free survival and overall survival (P = 0.013 and P = 0.002, log-rank test) compared with the high-PNI group. A significant positive correlation between PNI components including preoperative peripheral blood lymphocyte count and serum albumin concentration, and TILs, was observed. Absolute numbers of TILs in the preoperative high-PNI group were significantly increased compared with those in the preoperative low-PNI group (CD3+ cells; P = 0.002, CD4+ cells; P = 0.049 and CD8+ cells; P = 0.024). CONCLUSIONS The preoperative PNI level was strongly associated with the postoperative outcome in lung cancer patients. Considering the positive relationship between preoperative PNI level and TIL status, preoperative immune-nutritional condition may influence lung cancer patients’ postoperative prognosis through local immunity as well as systemic immune response.

Aim To evaluate the efficacy of chemotherapy with itraconazole for advanced or recurrent gastric cancer. Patients and methods Patients with human epidermal growth factor receptor 2 (HER2) negative unresectable gastric cancer referred to our hospital were included. The regimen comprised 160 mg/m2 nab-paclitaxel i.v. and 100 mg/m2 oxaliplatin i.v. on day 1, 60 mg/m2 S-1 orally on days 1-3, and 400 mg itraconazole orally on days -2 to 2, repeated every 2 weeks for 6-8 cycles. Results Twenty-three patients aged 40-80 years (median age=68 years) were enrolled, of whom 21 had stomach cancer and two gastroesophageal junction cancer. Regarding stage, two, one, and 20 patients had stage IIIA, IIIB, and IV, respectively. Among patients with liver metastases, 2/10 had simultaneous lung metastases. Nine patients had peritoneal dissemination, and five patients with stage IV disease developed recurrence after primary surgery followed by adjuvant S-1. The other 18 patients had no history of surgery or chemotherapy. The response rate was 70% (complete response in two; partial response in 14). Among 12 patients (67%) who underwent conversion surgery, R0 resection was conducted in eight, and no residual tumour was observed in two. For the population overall, the median overall survival was 24 months (95% confidence intervaI=21 months-not reached) and the 1-year overall survival rate was 95% (95% confidence intervaI=67-98%). Grade 3/4 neutropenia and grade 2 peripheral sensory neuropathy occurred in five (22%) and six (26%) patients, respectively, while no patient developed grade 3/4 thrombocytopenia. Conclusion Chemotherapy with itraconazole is promising for patients with unresectable gastric cancer.

Purpose Assessing microbiological culture results is essential in the diagnosis of empyema and appropriate antibiotic selection; however, the guidelines for the management of empyema do not mention assessing microbiological culture intraoperatively. Therefore, we tested the hypothesis that intraoperative microbiological culture may improve the management of empyema. Methods We performed a retrospective analysis of 47 patients who underwent surgery for stage II/III empyema from January 2011 to May 2019. We compared the positivity of microbiological culture assessed preoperatively at empyema diagnosis versus intraoperatively. We further investigated the clinical characteristics and postoperative outcomes of patients whose intraoperative microbiological culture results were positive. Results The positive rates of preoperative and intraoperative microbiological cultures were 27.7% (13/47) and 36.2% (17/47), respectively. Among 34 patients who were culture-negative preoperatively, eight patients (23.5%) were culture-positive intraoperatively. Intraoperative positive culture was significantly associated with a shorter duration of preoperative antibiotic treatment (p = 0.002). There was no significant difference between intraoperative culture-positive and -negative results regarding postoperative complications. Conclusions Intraoperative microbiological culture may help detect bacteria in patients whose microbiological culture results were negative at empyema diagnosis. Assessing microbiological culture should be recommended intraoperatively as well as preoperatively, for the appropriate management of empyema.

Leptomeningeal metastases (LM) may complicate the clinical course of any solid cancer or hematological malignancy. Diagnosis of such cases requires a multifaceted approach, including careful evaluation of the clinical history, detailed neurological examination, advanced imaging studies, and related laboratory data analysis. Therapeutic options for management of LM have not been standardized yet. Conventional intrathecal chemotherapy with or without involved-field fractionated radiotherapy has only modest efficacy, and the prognosis of most patients remains grim. Therefore, development of new, more aggressive multimodal treatment strategies is definitely needed. Immune checkpoint inhibitors-in particular, molecular targeted therapy-have demonstrated promising results in selected groups of patients. There may be an important role for stereotactic radiosurgery as well. Because organization of prospective randomized multi-institutional trials on treatment of LM of solid cancers may be problematic, practical guidelines for optimal therapeutic strategies in such cases should be established on the basis of integrated results of small-scale prospective and retrospective studies.

Aim of the study Recent advances in chemotherapy have increasingly enabled conversion surgery (CS) in patients with initially unresectable pancreatic cancer (PC), but patient selection remains controversial. We examined the characteristics of patients who would benefit from this procedure. Material and methods The clinical and pathological data of 38 patients with unresectable PC, who underwent CS after a favourable response to chemo(radio)therapy at our institute, were investigated. Univariate and multivariate analyses were performed to identify predictors for overall survival (OS). Several inflammation-based scores, such as the modified Glasgow prognostic score (mGPS), were also evaluated. Results The patients included 13 with locally advanced disease and 25 with metastatic disease. After non-surgical treatment with a median duration of six months, 27 patients (71%) underwent R0/1 resection, and the remainder underwent R2 resection. The two-year and five-year OS from the initial treatment for all patients were 64% and 29%, respectively, and the median survival was 29.1 months. Univariate analysis showed that age < 62 years, preoperative CA19-9 decrease rate ≥ 89%, preoperative mGPS-0, and R0/1 resection were related to a favourable OS. R0/1 resection and mGPS-0 were independent prognostic factors according to multivariate analysis. Conclusions Preoperative mGPS is a potential predictor of survival and can aid selection of patients for whom CS could yield promising prognosis for initially unresectable PC.

Anti-programmed-death-receptor-1 (anti-PD1) inhibitor, nivolumab, is an immune checkpoint inhibitor, which has recently been widely used and has become a standard treatment for various cancers, including non-small cell lung cancer and renal cell carcinoma. Nivolumab is known to induce various immune-related adverse effects (irAEs) in the lungs, skin, gastrointestinal tract, and endocrine organs. The most frequent irAEs of nivolumab were reported to be fatigue (34.2%), rush (25.9%), and diarrhea (19.2%).1 However, no report exists regarding the adverse effect of nivolumab on the urinary bladder. Here, we report two cases of nonbacterial cystitis after long-term nivolumab administration.

Background: Early recurrence (ER) after surgical resection is an important factor that impacts the survival of patients with pancreatic ductal adenocarcinoma (PDA). We examined risk factors for ER after PDA resection. Methods: One hundred and thirteen PDA patients who underwent R0 or R1 resection were retrospectively analyzed. Thirty-four patients (30.1%) received neoadjuvant chemotherapy (NAC) for borderline resectable (BR) (n=13) or initially unresectable (n=21) disease. ER was defined as that diagnosed within 6 months after surgery. Receiver operating characteristic analysis was performed for each variable to determine the optimal cutoff value. Results: ER occurred in 21 patients (18.6%). In univariate analysis, preoperative platelet-to-lymphocyte ratio (PLR) ≥144, carbohydrate antigen (CA) 19-9 ≥162 U/mL, and pathological tumor size ≥3 cm were significantly associated with ER. High PLR and CA19-9 were independent risk factors for ER by multivariate analysis. Area under the curve (AUC) for predicting ER from a combination of PLR and CA19-9 was 0.765 (95% confidence interval: 0.664–0.866), which increased the AUC compared to that for each risk factor alone. Patients with both risk factors had a significantly worse overall survival than those with one or no risk factors. When 24 patients with BR-PDA were considered, NAC was associated with a reduced likelihood of having risk factors and with a low ER rate. Conclusions: A combination of PLR and CA19-9 is a useful predictor of ER after macroscopic curative resection for PDA. NAC may reduce the risk of ER in selected patients.

Highlights • We assessed complications arising from the transfemoral, percutaneous implantation of an indwelling port–catheter system and described salvage of the system. • The catheter was salvaged by translating the subcutaneous pocket and changing the port and connecter or by removing the hematoma through an incision and applying ointment. • Salvage of the system may cause additional complications. Therefore, follow-up examination and a thorough consultation with an oncologist are required., Introduction Regional hepatic arterial infusion of chemotherapy is performed for unresectable liver tumors via percutaneously implanted port–catheter systems; while these port–catheter systems are effective administration routes, they are associated with various complications. Withdrawal of the system is considered if the complications occur, but repeated hepatic arterial infusion of chemotherapy (HAIC) via an implanted port–catheter system is a last-resort treatment for unresectable advanced liver cancer, and the treatment must be continued. We discuss various cases with complications arising in the indwelling port area in hepatic arterial infusion of chemotherapy and report whether the system was salvaged. Methods Between August 2013 and October 2017, eight patients (six males and two females) aged 61–80 years (mean age 76.6 years) with complications arising in a transfemoral indwelling port site for HAIC were referred to our department. All patients requested preservation of the system, especially the catheter. Each patient was assessed for the presence of “gross infection” based on a comprehensive evaluation of clinical findings and blood test results. In cases of “no gross infection,” we performed catheter salvage procedures. If there was no clinical improvement following the catheter salvage procedure, the port–catheter system was withdrawn. This research work has been reported in line with the PROCESS criteria. Results The port–catheter systems were withdrawn in two patients: one due to lasting infection and the other due to ulcer recurrence. Three cases were treated by removal of hematoma through an incision and ointment. The system was withdrawn in one of these cases due to exacerbation of ulcer; thus, the catheters were salvaged in five patients. None of these five patients experienced a relapse from 3 months to over 1 year after the procedure. Conclusion The success of subcutaneous HAIC significantly impacts a patient’s prognosis, especially for unresectable tumors and residual tumor recurrences. Initially, we chose to preserve the devices without removal, particularly if there was no infection. However, this approach led to a delay in chemotherapy, prolongation of healing time, and additional complications. These cases demonstrate the importance of a thorough consultation with the patient’s oncologist to discuss whether or not the device should be conserved.

Malignant transformation of hepatocellular adenoma (HA) is relatively rare and has been reported to be associated with dysregulation of the β-catenin pathway. The presence of bone marrow metaplasia in HA is an uncommon histological characteristic. The current report presents the case of a 46-year-old woman with glycogen storage disease type I (von Gierke's disease) who underwent resection of hepatocellular carcinoma (HCC) arising in a HA with associated bone marrow metaplasia producing three series of hematopoietic cells. The serum level of proteins induced by des-gamma-carboxy prothrombin (DCP) gradually increased as the tumors grew; following hepatic resection, DCP levels returned to normal. Nuclear accumulation of β-catenin was shown in HCC by immunohistochemistry; however, no mutation was detected in exon 3 of β-catenin. To the best of our knowledge, this is the first report of HA with absolute bone marrow metaplasia producing three series of hematopoietic cells. This occurrence suggests that elevated DCP may be an indicator of malignant transformation of HA.

4026 Background: Preclinical and clinical studies demonstrated that itraconazole, a common anti-fungal agent, has anticancer activity. The purpose of this study was to evaluate the efficacy of the chemotherapy with itraconazole on unresectable, metastatic, and recurrent gastric cancer. Methods: All patients were referred to our clinic with a clinical diagnosis of unresectable gastric cancer. The regimen consisted of 160 mg/m2 nab-paclitaxel IV on day 1, 100 mg/m2 oxaliplatin IV on day 1, 60 mg/m2 S-1 orally on days 1-7, and 400mg itraconazole orally on days -1 to 3, repeated every 3 weeks. Conversion surgery was allowed. The primary endpoint was overall survival (OS). Results: Between 2015 and 2018. 23 patients were enrolled. Their median age was 68 years (range 40-80 years); stomach/gastroesophageal junction: 21/2; Stage IIIA/IIIB/IV: 2/1/20. Among 10 patients who had liver metastases, 2 had simultaneous lung metastases. Nine patients had peritoneal dissemination. Five patients with stage IV had recurrent disease after primary surgery followed by adjuvant S-1. The other 18 patients had no history of surgery or chemotherapy. Response rate was 70% (CR/PR: 2/14). Among 12 patients (67%) who had conversion surgery, R0 resection was conducted in 8 and no residual tumor was observed in 2. Among enrolled 23 patients, median OS was 22 months (95%CI: > 12 months) and 1-year OS rate was 81.8% (95%CI: 46.7%―95.5%). Grade 3/4 neutropenia in 5 (22%), no grade 3/4 thorombocytopenia, grade 2 peripheral sensory neuropathy in 6 (26%). Conclusions: The addition of itraconazole to chemotherapy showed promising efficacy with high conversion surgery rate and with acceptable toxicities. Clinical trial information: UMIN000021340.

We evaluated the influence of the Hanshin-Awaji earthquake on the patients in our internal medicine department. After the initial rush of patients with injury, the number of respiratory diseases, largely pneumonia, increased within one month. This same event, however, seemed to decrease attacks among asthma patients. During the following three months, the number of peptic ulcer patients increased: 39.5% had a giant gastric ulcer and 34.8% had bleeding complications. Diabetic control of outpatients became worse after the earthquake. It is important to recognize that various disorders involving physical and psychological problems develop at different stages after a large-scale disaster.

An operative case of incrcerated femoral hernia associated with polycythemia vera (PV) is herein reported. A 76-year-old woman, who had been treated for PV with busulfan over the previous 7 years, developed an incarcerated femoral hernia and underwent partial resection of the small intestine along with herniorrhaphy under general anesthesia. The patient had been associated with severe bradycardia and malnutrition preoperatively, and also showed some mild respiratory failure postoperatively. However, the postoperative course was otherwise uneventful with no symptoms of disseminated intravascular coagulopathy or thrombosis, while prescribing a temporary pacemaker and intravenous administration of ulinastatin. The patient was discharged on the 15th postoperative day in good condition. Fifteen surgical cases of PV, including this case, have been reported in Japan and most of them were frequently accompanied with postoperative complications, which sometimes were fatal. Careful postoperative management of bleeding and any thrombotic complications therefore seems to be essential in successful management of the postoperative course in patients with polycythemia vera.

e15145 Background: The treatment of progressive biliary tract cancer (BTC) after first-line chemotherapy is under investigation. Itraconazole, a common antifungal agent, is a potent inhibitor of P-...

e15255 Background: The treatment of progressive pancreatic cancer after front-line chemotherapy is under investigation. Pretreated tumors express cancer stem cell markers and P-glycoprotein. Itraconazole, a common antifungal agent, is a potent inhibitor of the Hedgehog pathway, P-glycoprotein, and angiogenesis. We aimed to evaluate the efficacy and feasibility of chemotherapy with itraconazole for treating progressive pancreatic cancer. Methods: We retrospectively reviewed the medical charts of histologically diagnosed pancreatic cancer patients who had received one or more lines of chemotherapy and subsequent chemotherapy with itraconazole. The efficacy of itraconazole was evaluated according to the Response Evaluation Criteria in Solid Tumors, version 1.1 by considering the survival after chemotherapy with itraconazole. Results: Between 2008 and 2013, we enrolled 38 recurrent patients. All the patients were referred to our institution from tertiary care hospitals; they received docetaxel (35 mg/m2), gem...

Recent advances in imaging techniques such as dynamic intravenous contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) have enabled us to detect pancreatic cysts, some of which are potentially malignant. As the histopathological diagnosis cannot be confirmed preoperatively, enlarged pancreatic cysts are usually removed surgically. We report a rare case of pancreatic angiomatosis in a 21-year-old woman who presented with vague abdominal pain, a feeling of fullness, and nausea. Abdominal ultrasonography, contrast-enhanced CT, and MRI showed a huge mass in the right upper abdomen. We performed pylorus-preserving pancreato-duodenectomy, and the histopathological examination of the excised specimen revealed that the tumor was angiomatosis, probably originating from parapancreatic fibro-adipose tissue. She is doing well and has no evidence of recurrence 8 years after the operation. A complete surgical excision should be performed as curative treatment for pancreatic angiomatosis, which is an extremely rare disease when not associated with Von Hippel-Lindau syndrome.

Efficacy and safety of a newer injectable cephalosporin, cefluprenam (CFLP) on cases with bacterial pneumonia and chronic respiratory tract infections were evaluated at a dose of 1g (potency), d.i.d for 7 days. 1. Of 130 cases in total, 116 cases were enrolled for the clinical efficacy evaluation. The efficacy rate (excellent and good responses) was 94.8% (110/116). The efficacy rate was 93.8% (60/64) for cases with bacterial pneumonia, and 96.2% (50/52) for cases with chronic respiratory tract infections. The recurrence was noted in 1.2% (1/82). The bacteriological response rate was 100.0% (32/32) for gram positive cocci, 93.8% (15/16) for gram negative rods and 97.9% (47/48) in total. 2. Adverse drug reactions were noted in 3.9% (5/129), consisting of 2 cases with skin rash, 1 case with drug fever, 1 case with skin rash and skin itching and 1 case with drug fever and headache. The abnormal laboratory changes were noted in 23.6% (30/127), mainly containing the elevation in GPT and GOT, and eosinophylia. The safety rate (no problem evaluation) was 74.8% (95/127). 3. The usefulness rate (very useful and useful evaluations) was 93.1% (108/116). As suggested by the evaluation on the secondary endpoint in the phase III comparative studies with both bacterial pneumonia and chronic respiratory tract infections, it was confirmed that the 7 day therapy of CFLP was promising for treatment of moderate bacterial pneumonia and chronic respiratory tract infections, because the high clinical efficacy was obtained and also the incidence of allergic reactions with CFLP was almost the same as that of ceftazidime (CAZ) evaluated highly safe. Based on these results, it was concluded that CFLP was useful in the management of moderate respiratory tract infections and also the recommended therapeutic period with CFLP was within 7 days.

We report here three cases of squamous-cell carcinoma of the esophagus following endoscopic injection sclerotherapy for esophageal varices. All three patients were men and cigarette smokers, with a mean age of 58.3 +/- 5.0 years. Hepatitis B and C virus infection tests were negative, and alcoholic cirrhosis was present in each patient. The interval between sclerotherapy and the development of carcinoma was 9, 10, and 33 months, in the respective cases. The sclerosant used was 5% ethanolamine oleate with a mean total volume of 51.0 +/- 18.9 ml. While we have no evidence of a direct relationship between sclerotherapy and esophageal cancer, in patients with alcoholic cirrhosis who have risk factors for esophageal cancer there may be an acceleration of the potential malignancy, as a result of the chronic inflammation related to sclerotherapy. Such patients should be closely followed, using endoscopy.

A patient with reactive lymphoid hyperplasia of the liver was symptom free and had no underlying disease except for diabetes mellitus. The hepatic tumor was found by ultrasound examination at routine checkup. The preoperative diagnosis of the tumor was unsuccessful despite various radiological examinations. Histological examination of the resected tumor showed that it was composed of benign-appearing lymphocytic proliferations forming lymphoid follicles that included numerous germinal centers. The germinal center was mainly composed of B-cell marker, L26-positive lymphocytes, but a few T cells were also found. Lymphocytes surrounding germinal centers were mainly T-cell marker, UCHL1-positive T-cells, and a small number of B cells. The B cells in the lymphoid follicles were stained for both kappa and lambda light chains at equal frequency, indicating polyclonal and benign nature. A diagnosis of reactive lymphoid hyperplasia of the liver seems justified.

Twenty-one patients with hepatocellular carcinoma (HCC) larger than 10 cm diameter were treated during the 18year period from 1971 to 1988. The mean tumor size was 13 cm (range 10–18 cm). Nineteen patients (90.5%) had subjective symptoms. Eight patients (38.1%) had alpha-fetoprotein (AFP) levels over 10,000 ng/ml, and in 18 patients (85.7%) the levels were over 20 ng/ml. Nevertheless, only three (14.3%) were detected by AFP. Scintigraphy before 1981 and ultrasonography after 1982 appears to be most helpful for detection of HCC. Nineteen lesions (90.5%) were localized in the right hepatic lobe. Large HCC showed a low incidence of histologically verified concomitant cirrhosis (33%; 7 of 21) and a relatively well preserved hepatocellular function (indocyanine green test; 13.9 ± 6.6%). Curative resection could be done for all 21 patients. There were three (14.3%) operative deaths. The 1-, 3-, and 5-year survival rates were 72.2, 32.9, and 8.2%, respectively. One patient who underwent a left hepatic lobectomy has survived for over 5 years, with recurrence. There were 14 recurrences (66.7%) in 21 patients: 11 were hepatic and three were in the lungs. In patients with large HCC, surgical resection shoald be done, provided the clinical status and hepatocellular reserves are adequate. © 1992 Wiley-Liss, Inc.

To better comprehend the differences in deoxyribonucleic acid (DNA) content between a primary hepatocellular carcinoma (HCC) and pulmonary metastatic nodules, tissue specimens taken at autopsy of 25 patients who had not received any drugs to treat the malignancy were examined using microspectrophotometry. The DNA distribution patterns were classified into Types I–III, and low (Types I and II) or high (Type III) ploidies, according to DNA distribution. Changes in the DNA content from high to low ploidies, namely DNA ploidy reduction from the primary lesion to pulmonary metastatic lesions, was evident in 9 of the 25 patients (36%), and changes from low to high were noted in 2 of the 25 patients (8%). The remaining 14 (56%) showed no evidence of changes in the DNA ploidy pattern. Reduction of DNA ploidy seen in HCC and its metastatic lesions in the lung may be one of the aspects of clonal evolution or selection mechanisms during the progression of tumor growth and metastasis.

From September 1981 to December 1988, 163 patients underwent hepatic resection for hepatocellular carcinoma. The patients were divided into two groups: those operated on from September 1981 to March 1985 (n = 55) and those operated on from April 1985 to December 1988 (n = 705). There was an increase in the number of relatively small hepatocellular carcinomas in 1987–88. Differences in the incidence of accompanying liver cirrhosis (72 versus 62 per cent) were not statistically significant; however, values of the indocyanine green test (21·5 versus 77·0 per cent, P < 0·01) aided in strict patient selection. In more recent years, initial hepatic hilar dissection for control of vascular structures was undertaken and an ultrasonic dissector was used in about three-quarters of these patients. Consequently, the mean estimated blood loss (2500 versus 1300ml, P

Intrasplenic administration of OK-432, an immunostimulant derived from Streptococcus, prevented hepatic failure induced in rats by D-galactosamine. When OK-432 was given 1.0 K.E. (Group I) or 0.1 K.E. (Group II) into the subcutaneously transpositioned spleen three times prior to dosing with D-galactosamine, survival rates were 100 and 87%, respectively. On the contrary, with a splenic injection of saline (Group III), the survival rate was 47 and 32% in rats given OK-432 1.0 K.E. intraperitoneally (Group IV). The poisoned rats given no pretreatment (Group V) survived at a rate of 26%. These results show that intrasplenic administration of OK-432 leads to a significant enhancement of survival. Metabolic data and histological findings were compatible with survival rates, in each group. Activation of the reticuloendothelial function by the intrasplenic administration of this immunostimulant seems to have prevented acute liver failure.

Concentration of mast-cell precursors in hematopoietic tissues of mouse embryos was evaluated by a limiting dilution method. Cells from yolk sacs, livers, and bodies of (WB x C57BL/6)F1 (hereafter called WBB6F1)- +/+ embryos were injected directly into the skin of adult WBB6F1-W/Wv mice which were genetically depleted of tissue mast cells. Concentration of mast-cell precursors was calculated from the proportion of injection sites at which mast cells did not appear. Since the concentration of mast-cell precursors in the yolk sac was about 30 times as great as that of embryonic body at Day 9.5 of the pregnancy, the mast-cell precursors seemed to be generated within the yolk sac. The concentration in the yolk sac reached the maximum level at Day 11, and then dropped markedly at Day 13. In contrast, mast-cell precursors increased from Day 11 to Day 15 in the fetal liver. As a result, the concentration of 11-day yolk sacs was comparable to that of 15-day fetal liver. Although intravenous injection of 15-day fetal liver cells (2 x 10(6)) rescued the general mast-cell depletion of WBB6F1-W/Wv mice, the intravenous injection of the same number of 11-day yolk sac cells did not rescue it. In contrast with fetal livers, yolk sacs scarcely contained hematopoietic stem cells which were measured by spleen colony formation. Therefore, the mast-cell precursors of the yolk sac may not originate from such stem cells.

術後肝不全に対し高圧酸素療法が有効であった1例を報告する.症例は,57歳,男性,原発性肝癌にて右二圧域肝切除術な施行した.術後約1ヵ月目に肝性脳症を発症し直ちに血漿交換を行ったが,肝性脳症の改善は認められなかったため高圧酸素療法を施行した.本療法開始後,脳症は消失し.全身状態の改善も著明となり,第78病日に退院し得た.以上の経験は,高圧酸素療法が肝不全に対する新しい治療法となり得る可能性を示唆するものと考えられる.

We studied 36 cases (38 nodules) of small hepatocellular carcinoma with special attention directed to detectability using angiography and histology. Among the 38 nodules, 31 nodules (81.6%) were evident. The remaining seven (18.4%) were not evident angiographically but were detected using ultrasonography and/or computed tomography, prior to angiography. An elevated level of serum α-fetoprotein also suggested a diagnosis of hepatocellular carcinoma. When comparisons were made between angiographically detected and undetected nodules, there was no statistically significant difference in parameters, including sex of the patient, tumor size, location of the tumor, positive rate for hepatitis B surface antigen, history of liver disease and values of α-fetoprotein. The small hepatocellular carcinomas not detected angiographically and evidenced only histologically had the following characteristics: (i) no fibrous capsule surrounding the nodules; (ii) well-differentiated tumors; (iii) replacing growth pattern of cancer cells, and (iv) remains of portal tracts within the tumor. The replacing growth pattern and the presence of portal tracts may correlate with the low detectability in angiography. When a definite diagnosis of angiographically undetectable tumors cannot be made using close surveillance with ultrasonography or α-fetoprotein and/or needle biopsy under ultrasonic guide, surgical intervention should be considered, particularly for patients at high risk for hepatocellular carcinoma.

Cell nuclear DNA content was microspectrophotometrically measured in 60 specimens of clinical hepatocellular carcinoma (HCC). The DNA distribution pattern was classified into two types, diploid and nondiploid, according to the degree of dispersion on the DNA histogram. Among these 60 specimens, 26 had an HCC of less than 5 cm in diameter. In these 26, 17 (65%) had the diploid pattern and 9 (35%) had the nondiploid pattern. In the remaining 34 specimens with a large HCC exceeding 5 cm in diameter, the diploid pattern was seen in only six (18%), and the nondiploid pattern was seen in 28 (82%). Following increase in tumor size, the number of cases of nondiploid increased. The DNA pattern closely correlated with the morphologic grading and age of patients, yet there was no correlation among DNA pattern and presence of hepatitis B surface antigen (HBsAg) or presence of liver cirrhosis. Regarding the prognosis of patients with HCC, there was no statistic difference between DNA pattern and prognosis. The present study suggests that the DNA pattern relates to the biologic characteristics of the growth pattern of HCC. However, the DNA pattern showed no significant correlation with survival rates of patients with HCC who underwent hepatic resection.

Thirty-two patients with a solitary hepatocellular carcinoma of less than 4 cm diameter were treated during the 13 years from 1971 to 1983, two-thirds of them since 1981. Serum α-fetoprotein levels proved to be an excellent diagnostic tool for these early stage carcinomas which are generally asymptomatic. Ultrasonography forms an invaluable test for the detection of occult liver cancer and has enhanced the ability to detect small sized lesions. The accuracy of this method increased from 25 per cent for the period 1971-1980 to 89 per cent for the period 1981–1983. The cumulative survival rates for the 32 patients treated by hepatic resection at 1, 2 and 5 years were 85, 70 and 22.2 per cent (excluded from these figures are four operative deaths giving a 12.5 per cent operative mortality).

We treated a 67−year-old man with primary carcinoma and sarcoma arising from the different areas of the cirrhotic liver. Histologically the carcinoma was of hepatocellular origin and the sarcoma consisted mainly of poorly differentiated mesenchymal cells partly with a chondrosarcomatous component. Among nine similar cases reported in the literature, only one was a rhabdomyosarcoma and the others were described simply as of spindle cell variety without evidence of mesenchymal differentiation. In the present case, the sarcoma consisted of mesenchymal cells with distinctive areas of unequivocal chondrosarcoma. Acta pathol. jpn. 34: 919∼924, 1984.

Concentration of mast-cell precursors in the skin and liver of mouse embryos was evaluated by the limiting dilution analysis. The concentration of mast-cell precursors in the liver of (WB X C57BL/6)F1 (hereafter WBB6F1)-+/+ embryos reached the maximum level at Day 15 of the pregnancy, whereas the concentration in the skin at Day 17. The concentration of 17-day skin was about 10 times as high as that of 15-day liver. Appearance of morphologically identifiable mast cells in the skin followed the increase in concentration of the skin precursors. Concentrations of mast-cell precursors in the skin and liver of mutant embryos of Sl/Sld genotype were also measured to clarify the mechanism of mast-cell depletion in this mutant. Although the concentration of mast-cell precursors in the liver of WBB6F1-Sl/Sld embryos was comparable to that of the WBB6F1-+/+ embryos, the concentration in the skin of the Sl/Sld embryos was about 1% that of the +/+ embryos. Moreover, the concentration of morphologically identifiable mast cells in the skin of the Sl/Sld embryos was about 0.1% that of the +/+ embryos. Thus, mast-cell production in Sl/Sld embryos seemed to be suppressed at two stages; (1) during deficient invasion of liver-derived precursors into the skin, or the decreased proliferation of these cells, or both of these causes, (2) during differentiation of the precursors into mast cells.

In three patients with hepatocellular carcinoma (HCC), implanted metastases occurred in the peritoneal or pleural cavity after rupture of the tumors; in one patient this was caused by trauma, and in two others this complication became obvious during resection of the tumor. Hepatic resection was successful, and the postoperative status was satisfactory. Implanted metastases were present in the peritoneal or pleural cavity of these three patients 6 years, 10 months, and 6 months after surgery, respectively. We wish to emphasize that a ruptured HCC may lead to implanted metastases.

A case of dedifferentiated hepatocellular carcinoma with osteoclast-like giant cells resembling those of giant cell tumor of bone is presented. The clinicopathologic findings are described, and the literature concerning this type tumor is reviewed. The tumor differed histologically from a pleomorphic variant of hepatocellular carcinoma in that there were numerous osteoclast-like giant cells with numerous, small, uniform, benign-appearing nuclei. To the knowledge of the authors, there has been only one report of this type of tumor arising in the liver. The tumor contained a separate area of a histologically conventional hepatocellular carcinoma, in addition to the above giant cell areas.