Effect of oxaliplatin-based chemotherapy on chemosensitivity in patients with peritoneal metastasis from colorectal cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: proof-of-concept study.

BACKGROUND: Chemosensitivity testing, including collagen gel droplet-embedded culture drug sensitivity test, has proven to be a useful tool in therapeutic decision-making. This retrospective analysis investigated chemosensitivity testing of peritoneal metastases collected during cytoreductive surgery (CRS), and its impact on survival in patients with colorectal cancer. METHODS: All patients with peritoneal metastasis from colorectal cancer who underwent CRS with or without hyperthermic intraperitoneal chemotherapy (HIPEC) between November 2008 and October 2014 were included. The growth inhibition rate was expressed as the ratio between the image density after treatment (T) and that before treatment (control, C). Tumours with a reduction in T/C ratio of less than 20 per cent were defined as resistant and those with a reduction of 20 per cent or more as sensitive. Groups were compared for overall (OS) and disease-free (DFS) survival. RESULTS: Of 84 eligible patients, 81 received neoadjuvant chemotherapy (NACT), including 56 patients with an oxaliplatin-based regimen. Mean(s.d.) follow-up was 23·4(22·9) months. The median overall survival of all patients was 19·0 (i.q.r. 5·7-36·1) months, with a progression-free survival time of 10·1 (4·5-17·0) months. Patients who received oxaliplatin-based NACT had significantly altered chemosensitivity to oxaliplatin; only 20 of 51 such patients showed chemosensitivity to oxaliplatin compared with 16 of 24 who did not undergo oxaliplatin-based NACT (P = 0·046). However, patients who showed chemoresistance to oxaliplatin had similar OS to those with chemosensitivity (18·8 versus 18·1 months; P = 0·835). The choice of HIPEC agents in patients who received oxaliplatin-based NACT did not significantly influence survival (oxaliplatin versus mitomycin C: median OS 20·6 (10·9-24·8) versus 19·0 (10·5-34·6) months, P = 0·811; DFS 6·6 (2·8-25·7) versus 9·3 (4·1-13·9) months, P = 0·191). CONCLUSION: Patients who had oxaliplatin-based NACT showed a higher rate of chemoresistance to oxaliplatin at the time of CRS and HIPEC. The impact of chemosensitivity testing on OS remains unclear and needs further investigation.

A comparison of the Pentax Airway Scope™ with the Airtraq™ in an infant manikin.

We compared the Pentax Airway Scope(TM) with the Airtraq(TM) optical laryngoscope in an infant manikin. Twenty-three anaesthetists randomly performed tracheal intubation: at rest, (a) with the Airway Scope and (b) with the Airtraq; and during chest compressions, (c) with the Airway Scope and (d) with the Airtraq. The success rate, modified Cormack and Lehane classification for glottic view, time taken to view the glottis, and time to place the tracheal tube were recorded. There was no difference in intubation success rate or quality of glottic view between the two devices. The median (IQR [range]) time taken to obtain a view of the glottis was 4.5 (3.7-6.4 [1.8-14.0]) s using the Airway Scope compared with 7.1 (5.5-9.6 [3.3-12.0]) s using the Airtraq (p = 0.001), and to successful placement of the tracheal tube was 8.3 (6.8-9.4 [3.7-20.7]) s using the Airway Scope compared with 11.2 (10.4-13.8 [4.9-23.7]) s using the Airtraq (p = 0.001). During chest compressions, the median (IQR [range]) time taken to view the glottis was 5.1 (4.0-7.2 [2.0-12.4]) s using the Airway Scope compared with 7.5 (5.0-13.2 [4.2-26.4]) s using the Airtraq (p = 0.006), and to successful placement of the tracheal tube was 9.5 (6.6-13.7 [4.5-16.2]) s using the Airway Scope compared with 11.7 (9.1-18.1 [6.2-37.4]) s using the Airtraq (p = 0.022). We conclude that both devices provided good quality views of the glottis and successful tracheal intubation in an infant manikin both at rest and during external chest compressions. Use of the Airway Scope resulted in a shorter time to view the glottis and perform successful tracheal intubation compared with the Airtraq.

Subaru telescope observations of Deep Impact.

The impact cratering process on a comet is controversial but holds the key for interpreting observations of the Deep Impact collision with comet 9P/Tempel 1. Mid-infrared data from the Cooled Mid-Infrared Camera and Spectrometer (COMICS) of the Subaru Telescope indicate that the large-scale dust plume ejected by the impact contained a large mass (approximately 10(6) kilograms) of dust and formed two wings approximately +/-45 degrees from the symmetric center, both consistent with gravity as the primary control on the impact and its immediate aftermath. The dust distribution in the inner part of the plume, however, is inconsistent with a pure gravity control and implies that evaporation and expansion of volatiles accelerated dust.

Hepatobiliary cystadenoma combined with multiple liver cysts: report of a case.

Hepatobiliary cystadenomas are rare benign tumors with malignant potential. They are almost always solitary lesions accompanied by multilocular cysts in the liver, and are difficult to differentiate from cystadenocarcinoma, despite the diagnostic modalities available. This report describes a case of hepatobiliary cystadenoma with multiple cysts in the left hepatic lobe, diagnosed by magnetic resonance imaging in a 48-year-old woman. Abdominal computed tomography revealed only multiple cystic lesions in the left lobe, but cholangiography via a nasogastric biliary drainage tube combined with percutaneous transhepatic cholangiography showed a stenotic region with fine irregularity in the left lateral posterior segmental bile duct and left lateral anterior segmental bile duct. Hepatobiliary cystadenocarcinoma with multiple liver cysts was suspected. We performed left hepatectomy, and microscopic examination confirmed a diagnosis of hepatic cystadenoma with multiple liver cysts. There was no nuclear atypia or mitosis in the epithelium of the locus, which was constructed of simple columnar-to-cuboidal epithelium with basal nuclei. The patient is well without recurrence more than 4 years after surgery.

Surgical treatment for non-dilated biliary tract with pancreaticobiliary maljunction should include excision of the extrahepatic bile duct.

BACKGROUND/AIMS: The authors evaluated the surgical treatment for non-dilated biliary tract with pancreaticobiliary maljunction. METHODOLOGY: Sixty-nine patients with pancreaticobiliary maljunction were divided into 61 patients with the dilated biliary tract and 8 with the non-dilated biliary tract. The levels of amylase activity in the bile in the gallbladder and the bile duct, the incidence and severity of postoperative cholangitis, and cell proliferating activity of the biliary tract epithelium, examined the proliferating cell nuclear antigen labeling index (PCNALI), were examined. RESULTS: Of the 61 dilated type patients, 12 were of Ia, 1 was of Ib, 22 were of Ic, 25 were of IV-A, and 1 was of IV-B according to Todani's classification. Cancer was detected in 7 dilated type patients and in 3 non-dilated type patients. A high level of amylase activity was measured in the bile juice in both the gallbladder and bile duct in all of the patients with pancreaticobiliary maljunction. PCNALI of the biliary tract epithelium of the patients without cancer (dilated type: bile duct 11.4%, gallbladder 12.7%; non-dilated type: bile duct 5.9%, gallbladder 13.8%) was higher than that of the patients without pancreaticobiliary maljunction (bile duct 1.5%, gallbladder 1.4%). CONCLUSIONS: In a non-dilated type, as well as in a dilated type, a high level of amylase activity and increase of cell proliferative activity of the biliary tract epithelium were observed. Therefore, these results suggest that the extrahepatic bile duct should be prophylactically removed in patients with non-dilated type as well as in those with dilated type pancreaticobiliary maljunction.

Surgical treatment for congenital biliary dilatation, with or without intrahepatic bile duct dilatation.

BACKGROUND/AIMS: The incidence of postoperative cholangitis differs between patients with and those without congenital intrahepatic bile duct dilatation. The aim of this study was to evaluate comparatively the treatment results in these two patients groups. METHODOLOGY: Forty-eight patients were classified into those with (dilated type) and those without (nondilated type) intrahepatic bile duct dilatation. The surgical procedure used, clinical manifestation, and cell kinetics (proliferating cell nuclear antigen labeling index, PCNALI) of bile duct epithelium were examined with respect to the incidence and course of postoperative cholangitis. RESULTS: Nineteen patients were classified as the dilated type, and the other 29 patients were the nondilated type. In the dilated-type group, hepaticoduodenostomy was performed on five patients, hepaticojejunostomy (Roux-en-Y method) on eight and jejunal interposition on six. Among the 29 nondilated-type patient, hepaticoduodenostomy was performed on 19 patients, hepaticojejunostomy (Roux-en-Y method) on seven, and jejunal interposition on three. Hepatectomy was performed in one dilated-type adult patient with marked cholangiectasia in the left hepatic lobe. The incidence of postoperative cholangitis was 26.3% (5/19) in the dilated-type group and 6.9% (2/29) in the nondilated-type group. The clinical manifestation was generally mild in the nondilated-type patients. However, among the adult dilated-type patients, on whom jejunal interposition had been performed, there were two patients who required additional surgery for the treatment of cholangitis that occurred postoperatively. The PCNALI in the bile duct epithelium was 13.9% for the dilated-type and 8.8% for the nondilated-type groups, respectively. CONCLUSIONS: Jejunal interposition for biliary reconstruction seems a contraindicated maneuver for adult dilated-type patients, because of the possible development of postoperative cholangitis. The cellular proliferating activity in the bile duct epithelium of the patients of both the dilated and nondilated type was significantly increased compared to that of a control group. Consequently, the extrahepatic bile duct might have to be removed in patients with pancreaticobiliary maljunction regardless of the presence or absence of biliary dilatation.

Primary effusion lymphoma with B-cell phenotype.

We describe here a case of primary effusion lymphoma that occurred in a 78-year-old woman. She was successively treated with prednisolone but died 15 months after the diagnosis of primary effusion lymphoma. The immunohistochemistry revealed the neoplastic cells to be CD19(+), CD20(+), CD21(+), Sm-Ig(+), and HLA-DR(+). This patient exhibited clonal IgH and clonal kappa light chain gene rearrangement, indicating a B-cell origin. The present case was distinguished from the majority cases of HHV-8-positive primary effusion lymphoma. Here we present clinical details of response to therapy in this case.

Advanced gallbladder carcinoma with liver metastasis showing a favorable response after intra-arterial infusion chemotherapy: report of a case.

A 66-year-old woman visited a local clinic due to general fatigue. After undergoing examinations at our hospital, the patient was diagnosed to have advanced gallbladder carcinoma with metastasis to the liver and cholecystolithiasis, After receiving a cholecystectomy, we performed chemotherapy by the intra-arterial infusion of low-dose cisplatin and 5-fluorouracil via hepatic artery, and observed its marked effect on the tumors by computed tomography. The level of carcinoembryonic antigen decreased from 114.5 ng/ml to 0.8 ng/mg, and carbohydrate antigen 125 decreased from 1 094 U/ml to 75 U/ml. The present result suggests that this therapy may be useful for some selected patients with an advanced gallbladder carcinoma.

Evaluation of treatment strategies for gastric cancer in the elderly according to the number of abnormal parameters on preoperative examination.

The treatment strategies in patients with gastric cancer aged 80 years or older have not yet been well defined. We examined the incidence of postoperative complications and hospital mortality regarding the preoperative condition of such patients. A preoperative examination included evaluations of the cardiac, pulmonary, renal, and hepatic functions, the presence or absence of anemia, nutritional status, and blood sugar content. The incidence of postoperative complications and hospital mortality were then studied in relation to the number of preoperative abnormal parameters. The incidence of postoperative complications was 37.0%. The rate of hospital mortality was 11.1%. Among the patients with abnormalities in five or more items, the incidence of complications was 76.9% and the rate of hospital mortality was 23.1%. In the patients with an operative time of 4 h or longer, the same incidence was 71.4%. Among the patients who underwent a curative resection, the 5-year survival rate was 92.3%. For elderly gastric cancer patients with abnormalities in five or more items during a preoperative examination and for those showing a poor level of daily life activity, a less invasive treatment modality should be planned. Patients with abnormalities of four or fewer items at a preoperative examination appear to be good candidates for curative resection.

The relationship between levels of neutrophil-related factors and the degree of surgical stress.

To find a method for estimating the degree of surgical stress, 53 patients were divided into 3 groups according to operation time (group I, > or =5 h or more; group II, 1-4 h; and group III, <1 h) and measurement of neutrophil-related factors was performed. The postoperative levels of chemiluminescence (CL) generated by neutrophils (5.5 x 10(8)cpm) in group I was significantly higher than that in group II (2.1 x 10(8)cpm). The postoperative levels of CL in whole blood (5.7, 2.9, 1.0 x 10(6)cpm for groups I, II and III, respectively) and plasma lactoferrin levels (Lf) (653, 302, 143 ng/ml) were highest in group I and lowest in group III. The serum iron (Fe) level (24, 32, 58 microg/dl for groups I, II, III) was highest in group III and lowest in group I. In conclusion, whole blood CL, neutrophil CL, Lf and Fe levels after surgery can be useful indicators of the degree of surgical stress.

Clinical evaluation of lymph node metastasis in gastric cancer defined by the fifth edition of the TNM classification in comparison with the Japanese system.

BACKGROUND: This study compared the classification of lymph node metastasis according to the number of involved nodes based on the new tumour node metastasis (TNM) system (fifth edition) with the classification by the Japanese Research Society for Gastric Cancer from an anatomical perspective. METHODS: The two classifications were related to long-term results in 1489 patients with gastric cancer who underwent gastrectomy with systematic extended lymphadenectomy. RESULTS: Both classifications performed well as prognostic indicators (5-year survival rates: pathological (p) N0, 89 per cent; pN1, 66 per cent; pN2, 34 per cent; pN3, nil; and M1, 10 per cent by the TNM classification; n0, 89 per cent; n1, 63 per cent; n2, 46 per cent; n3, 20 per cent; and n4, 8 per cent by the Japanese classification). For regional lymph nodes, the TNM classification was a better index of the prognosis. Significant survival differences were observed among patients with M1 disease according to the number of involved lymph nodes (between one and six nodes, 48 per cent; seven to 15 nodes, 12 per cent; more than 15 nodes, 2 per cent), indicating that patients with distant metastatic lymph nodes (M1) should also be classified by the number of involved nodes. On the other hand, the Japanese classification has the added benefit of being a good indicator of the anatomical extent of lymphadenectomy. CONCLUSION: The new TNM classification provided a better index of the prognosis of patients who underwent systematic lymph node dissection. However, both classifications have specific benefits in the surgical treatment of gastric cancer.

Cystic lymphoepithelial lesions of the pancreas and peripancreatic region: report of two cases.

Two cases of an extremely rare cystic lymphoepithelial lesion of a lymph node associated with the pancreas are presented herein. The first patient was a 57-year-old woman with a serous cystoadenoma who underwent resection of the body and tail of pancreas, and the other patient was a 75-year-old woman with cancer of the papilla of Vater who underwent pylorus-preserving pancreatoduodenectomy. Both lesions were incidentally found during pathologic examination of lymph nodes from the peripancreatic region. Histologically, there were many scattered nests of the lymphoepithelial lesion in the lymphoid stroma, each of which was lined with stratified squamous epithelium. The pathological structure was found to resemble the lymphoepithelial lesion of the pancreas. Although the histogenesis is unknown, we hypothesize that the lesion might have arisen from squamous metaplasia of a benign epithelial inclusion such as the pancreatic duct of an ectopic pancreas in a peripancreatic lymph node. Therefore, a cystic lesion formed as a result of keratinization of the squamous epithelium with invasion into the pancreas could become a lymphoepithelial cyst of the pancreas.

Prognostic value of tumor cell proliferation and intratumor microvessel density in advanced gastric cancer treated with curative surgery.

To clarify the prognostic value of tumor cell proliferation [proliferating cell nuclear antigen (PCNA)-positive rate assessed by anti-PCNA immunostaining] and intratumor microvessel density (/0.74 mm2, assessed by anti-CD34 immunostaining) in gastric cancer, 192 advanced gastric cancer patients who underwent curative surgery were investigated. Multivariate analysis showed that the following variables were significantly related to prognosis: age (P=0.029), depth of invasion (P=0.005), lymph node metastasis (P=0.006), lymphatic invasion (P=0.038), venous invasion (P=0.0005), PCNA-positive rate (P=0.049) and intratumor microvessel density (P=0. 011). In conclusion, tumor cell proliferation and intratumor microvessel density were independent prognostic factors in patients with advanced gastric cancer undergoing curative surgery.

Varicella and varicella immunity in patients with lysinuric protein intolerance.

Two patients with lysinuric protein intolerance (LPI) had near-fatal generalized varicella infection with severe interstitial pneumonitis, hepatitis, decreased platelet count, bleeding and hypoalbuminaemia. Active haemolysis resulted in anaemia and massive haemoglobinuria. Serum lactate dehydrogenase activity and ferritin concentration, which in patients with LPI in normal circumstances exceed the upper reference values 3-folds to 10-fold, increased to > 10,000 U/L and > 10,000 micrograms/L, respectively. The patients were treated with fresh frozen plasma, red-cell transfusions and intravenous acyclovir for 14 days, and recovered clinically in a month. Retrospectively, 3 of the 32 other known Finnish patients with LPI had had varicella infection that had been more severe than that in the other children in the family or in subjects in the neighbourhood and had led to hospital admission. Varicella antibodies were measured in 24 patients; 5 had no antibodies and 5 had very low antibody titres. Primary vaccination of three patients with living varicella vaccine increased antibody titres measurably in one patient. We suggest that patients with LPI who have no varicella zoster antibodies should be treated with acyclovir if exposed to varicella and should be (re)vaccinated against chickenpox.

Proliferating cell nuclear antigen expression in the gallbladder with pancreaticobiliary maljunction.

BACKGROUND AND OBJECTIVE: To clarify the histogenesis of cancer of the gallbladder of the patients with pancreaticobiliary maljunction (PBMJ), the proliferating cell activity of the epithelium of gallbladder was examined. METHODS: A total of 21 patients with pancreaticobiliary maljunction [8 with gallbladder cancer (MCA group) and 13 without cancer (M group)] were studied using immunohistochemical staining with a monoclonal antibody to the proliferating cell nuclear antigen (PCNA). The 23 gallbladder cancer patients without PBMJ (CA group) and 10 patients with normal gallbladders (N group) were also examined as controls. RESULTS: The PCNA-positive rates of non-cancerous epithelium of the gallbladder in patients with PBMJ (14.2% in MCA group and 11.6% in M group) were significantly higher than those without PBMJ (3.9% in CA group and 1.5% in N group). CONCLUSION: The high proliferating cell activity of epithelium of the gallbladder may be an explantation for the high incidence of gallbladder cancer in patients with pancreaticobiliary maljunction.

Multiple early gastric carcinomas. Clinicopathologic features and histogenesis.

BACKGROUND: Multiple early gastric carcinomas were found in 5-15% of patients with early gastric carcinoma. The goals of this study were to clarify the clinicopathologic features of multiple early gastric carcinomas and to investigate their histogenesis. METHODS: Of 724 patients with early gastric carcinoma, there were 65 with multiple (159) gastric carcinomas. Investigation of the histogenesis of multiple gastric carcinomas was conducted using serial sections of the stomach of 33 patients with multiple early gastric carcinomas (MEGC) and 33 patients with solitary early gastric carcinoma (SEGC). The cancerous and epithelial dysplastic lesions were examined by hematoxylin and eosin staining and immunohistochemical staining of p53 protein with anti-p53 monoclonal antibody (BP53-12). RESULTS: The macroscopically depressed type was common. The flat type was observed only in accessory lesions, most of which were diagnosed postoperatively. There were 126 differentiated type lesions, and 33 poorly differentiated type lesions. In most cases both the main and accessory lesions were differentiated. The average number of epithelial dysplastic lesions (18.3) in the stomach of patients with differentiated MEGC was significantly higher than that in the stomach of patients with differentiated SEGC (7), poorly differentiated MEGC (2.1), and SEGC (2). Moreover, severe dysplastic lesions were frequently observed in the stomach of patients with differentiated MEGC. p53 protein expression was detected in 0.9% of mildly atypical epithelial dysplastic lesions, 3.7% of moderately atypical dysplastic lesions, and 18.2% of severely dysplastic lesions. CONCLUSIONS: In cases of early gastric carcinoma, small depressed type and flat type accessory lesions of multiple gastric carcinomas should be detected preoperatively. Epithelial dysplastic lesions probably are significant in the histogenesis of differentiated multiple gastric carcinomas.

[Preoperative diagnosis and surgical treatment for lymph node metastasis in gastric cancer].

In order to clarify the preoperative diagnostic ability for lymph node metastasis, images from magnetic resonance imaging (MRI), computed axial tomography (CT) and ultrasonography (US) were evaluated in 200 gastric cancer patients. The long-term results of 2,000 gastric cancer patients who had undergone gastrectomy were also studied to evaluate the effectiveness of lymphadenectomy. 1) Preoperative diagnosis of lymph node metastasis: The detection rate of lymph nodes around the stomach was 34.1% in MRI, 18.7% in CT and 5.0% in US. The incidence of metastasis was over 80% when the size of lymph node imaged was 1.5 cm and over, against 25% for lymph nodes less than 1.0 cm in size. The detection rate of metastatic lymph node according to the mode of metastasis was 88% for macro-nodular type, 66% for micro-nodular type, 57% for diffuse type in MRI, 70, 41 and 15% in CT, and 38, 3, 0% in US, respectively. Therefore, MRI was most useful for detecting metastatic lymph node preoperatively. 2) Long-term results of gastric cancer with lymph node metastasis: The cumulative 5-year survival rate was 84.2% in n0, 56.1% in n1, 33.7% in n2, 16.5% in n3, and 5.1% in n4 patients. Satisfactory long-term results were obtained for n2 or less patients without serosal invasion. Moreover, by paraaortic lymph node dissection, the cumulative 5-year survival rate in n4 patients was 16.4% (27.8% for cases with radical resection). These results showed the effectiveness of lymph node dissection for gastric cancer.