Risk Factors for Difficult Laparoscopic Cholecystectomy in Acute Cholecystitis.

BACKGROUND AND OBJECTIVES: Factors that contribute to difficult laparoscopic cholecystectomy (LC) in acute cholecystitis (AC) that would affect the performance of early surgery remain unclear. The purpose of this study was to identify such risk factors. METHODS: One hundred fifty-four patients who underwent LC for AC were retrospectively analyzed. The patients were categorized into early surgery and delayed surgery. Factors predicting difficult LC were analyzed for each group. The operation time, bleeding, and cases of difficult laparoscopic surgery (CDLS)/conversion rate were analyzed as an index of difficulty. Analyses of patients in the early group were especially focused on 3 consecutive histopathological phases: edematous cholecystitis (E), necrotizing cholecystitis (N), suppurative/subacute cholecystitis (S). RESULTS: In the early group, the CDLS/conversion rate was highest in necrotizing cholecystitis. Its rate was significantly higher than that of the other 2 histopathological types (N 27.9% vs E and S 7.4%; P = .037). In the delayed-surgery group, a higher white blood cell (WBC) count and older age showed significant correlations with the CDLS/conversion rate (P = .034 and P = .004). CONCLUSION: In early surgery, histopathologic necrotizing cholecystitis is a risk factor for difficult LC in AC. A higher WBC count and older age are risk factors for delayed surgery.

Surgical resection of solid gallbladder adenocarcinoma presenting as a large mass: report of a case.

This report describes a case of a patient with a large solid gallbladder adenocarcinoma that was completely resected through aggressive surgery. The patient was a 57-year-old woman who had been diagnosed with advanced gallbladder cancer, had no indications for surgical resection and was scheduled to undergo systemic chemotherapy. She presented to our hospital for a second opinion. At the time of assessment, her tumor was large but was well-localized and had not invaded into the surrounding tissues, indicating that surgical resection was a reasonable option. Subsequently, the tumor was completely extracted via right hepatectomy with en bloc resection of the caudate lobe and extrahepatic bile duct. Histopathologically, the tumor was a solid adenocarcinoma. Although there are relatively few reports in the literature regarding solid gallbladder adenocarcinoma, well-localized growth appears to be a characteristic feature. On the basis of a tumor's progression behavior, aggressive surgical treatment might be indicated even when the tumor has grown to a considerable size.

Blood stasis may cause thrombosis in the left superior pulmonary vein stump after left upper lobectomy.

BACKGROUND: We previously reported that arterial infarction of vital organs after lobectomy might occur only after left upper lobectomy and be caused by thrombosis in the left superior pulmonary vein stump. We hypothesized that changes in blood flow, such as blood stasis and disturbed stagnant flow, in the left superior pulmonary vein stump cause thrombosis, and this was evaluated by intraoperative ultrasonography. METHODS: From July 2013 to April 2014, 24 patients underwent lobectomy in the Steel Memorial Muroran Hospital. During the procedure, an ultrasound probe was placed at the pulmonary vein stump and the velocity in the stump was recorded with pulse Doppler mode. The peak velocity and the presence of spontaneous echo contrast in the stump were evaluated. After the operation, the patients underwent contrast-enhanced CT within 3 months. RESULTS: The operative procedures were seven left upper lobectomies, four left lower lobectomies, seven right upper lobectomies, and six right lower lobectomies. Blood flow was significantly slower in the left superior pulmonary vein stump than in the right pulmonary vein stumps. However, that was not significantly slower than that in the left inferior pulmonary vein stump. Spontaneous echo contrast in the pulmonary vein stump was seen in three patients who underwent left upper lobectomy. Of the three patients with spontaneous echo contrast, two patients developed thrombosis in the left superior vein stump within 3 months after the operation. There was no patient who developed arterial infarction. CONCLUSIONS: In patients who underwent left upper lobectomy, intraoperative ultrasonography to evaluate blood flow and the presence of spontaneous echo contrast in the left superior pulmonary vein stump may be useful to predict thrombosis that may cause arterial infarction.

Left upper lobectomy can be a risk factor for thrombosis in the pulmonary vein stump.

BACKGROUND: Thrombosis in the left upper pulmonary vein stump after left upper lobectomy is a very rare but important complication because it occurs in the systemic circulation system. We previously made the first ever report on the frequency and risk factors of thrombosis in the pulmonary vein stump after lobectomy. In this study, we conducted an investigation in a different hospital to determine whether this was a common complication. METHODS: From 2008 to 2012, 151 patients who underwent lobectomy and following enhanced CT within 2 years after the operation were studied. Postoperative contrast-enhanced CT imaging was retrospectively checked. RESULTS: We found thrombosis in the pulmonary vein stump in 5 of the 151 patients (3.3%). All 5 patients underwent left upper lobectomy (17.9% of the patients who underwent left upper lobectomy). These 5 patients did not have infarction of any vital organ. The thrombus was disappeared several months later on contrast-enhanced CT in 3 patients and followed in 2 patients. On univariate analysis, there was a significant difference only in the operative procedure (p<0.001). CONCLUSIONS: Thrombosis in the pulmonary vein stump occurred with high frequency in patients who underwent left upper lobectomy. Because the frequency of thrombosis in this study was the same as in our previous report, this might be a common complication.

Ganglioneuroblastoma arising within a retroperitoneal mature cystic teratoma.

We discuss an extremely rare case of ganglioneuroblastoma arising within a retroperitoneal mature cystic teratoma. Radiological examinations showed a cystic tumor sandwiched between the pancreas and left kidney. Surgery was scheduled because the tumor seemed to have originated from the pancreas. En-block resection of the tumor with distal pancreatectomy, splenectomy, and left adrenalectomy was performed. In terms of macroscopic appearance, the tumor mainly consisted of a unilocular cystic mass, but the presence of a smaller, solid mass was also noted within the tumor. Histopathologic examination confirmed that the cystic mass was consistent with a mature cystic teratoma of the retroperitoneum, and in addition, a ganglioneuroblastoma was evident in the solid component. Histopathologically, the ganglioneuroblastomatous area was intimately associated with dermoid tissue of the mature cystic teratoma, thus this case was diagnosed to be a mature cystic teratoma with malignant transformation. To best of our knowledge, this is the first reported case of ganglioneuroblastoma arising in a mature cystic teratoma.

Metachronous pancreatic acinar cell carcinoma discovered in early stage during follow-up of breast cancer: report of a case.

We present an extremely rare case of early-stage acinar cell carcinoma of the pancreas. A 49-year-old woman, who had undergone radical surgery for breast cancer 3 years earlier, was suspected to have a rib metastasis during follow-up. She also had a family history of cancer. No accumulation was seen in the left rib on (18)F-fluorodeoxyglucose positron emission tomography with computed tomography, but incidental high uptake into the pancreatic head suggested malignant pancreatic tumor. The tumor was completely resected by pancreatoduodenectomy, and pancreatic acinar cell carcinoma was demonstrated histopathologically. To the best of our knowledge, this is the first reported case of a pancreatic acinar cell carcinoma smaller than 1 cm to be detected by (18)F-fluorodeoxyglucose positron emission tomography and computed tomography.

Goblet cell carcinoid of the rectum with lymph node metastasis: report of a case.

We report an unusual case of goblet cell carcinoid (GCC) of the rectum. A 75-year-old man was admitted to our hospital with anal bleeding, and a hard tumor was felt on the anterior wall of the lower rectum during rectal examination. We performed colonoscopy, and found a 30-mm type 2 tumor in the lower rectum and anal canal. Histological examination of biopsies revealed rectal adenocarcinoma. Based on these findings, we diagnosed rectal adenocarcinoma and performed Miles' operation with lymph node dissection. Histological examination revealed an invasive lesion composed of signet-ring-like cells. Seven regional lymph node metastases were seen microscopically. The tumor produced copious mucin, which was stained with Alcian blue. Immunohistochemistry was positive for synaptophysin, chromogranin A, CD56, carcinoembryonic antigen, p53, Ki-67, E-cadherin, and cytokeratin 20. The final diagnosis was GCC of the rectum.

[A case of emergency operation for pedicle torsion of ovarian tumor during bevacizumab therapy].

We report a case of torsion of ovarian carcinoma pedicle during chemotherapy with bevacizumab and FOLFIRI. A 47-year-old-female who had undergone laparoscopic-assisted sigmoidectomy for sigmoid cancer with multiple metastatic liver tumors, was treated with 3 courses of FOLFOX4 and 9 courses of FOLFIRI. Bevacizumab (BV) was started to administer with FOLFIRI since a CT scan had revealed that metastatic liver tumors had enlarged . Four days after final administration of BV (13th course), she presented lower abdominal pain. CT scan showed an enlarged right ovary sized 20 cm, but no findings suggesting bowel perforation; therefore we assumed her pain was due to enlarged ovarian tumor, which might be metastasis from sigmoid cancer. Increased oral morphine could not relieve her pain. Then, along with sufficient information about the risks of the operation caused by BV, we proposed an operation to remove her enlarged ovary. Day 16 after final administration of BV, we undertook a laparotomy by lower median incision, and found a twisted right adnex with large necrotic ovarian tumor. Pathologists diagnosed the ovarian tumor as primary ovarian cancer. No complication related to BV occurred, and she was moved to the ward for internal medicine 13 days after operation.

Esophageal carcinosarcoma presenting as a fever with elevated serum interleukin-6.

We report a patient with esophageal carcinosarcoma who initially presented with fever. A 57-year-old man with a 4-month history of intermittent fever was referred to our hospital and diagnosed as having esophageal carcinosarcoma. High fever persisted and serum concentration of interleukin-6 was markedly elevated. In contrast, after thoracic esophagectomy, the fever subsided and interleukin-6 serum levels rapidly normalized. The clinical course of the patient suggests that the tumor produced interleukin-6 and this was associated not only with inflammation, but also the aggressive biologic behavior of the tumor.

Imaging of acquired cystic disease-associated renal cell carcinoma by contrast-enhanced ultrasonography with perflubutane microbubbles and positron emission tomography-computed tomography.

The preoperative assessment of renal cell carcinoma (RCC) complicated with acquired renal cystic disease in a 63-year-old male patient on long-term hemodialysis (30 years and 8 months) that was difficult because of no or poor contrast enhancement by dynamic CT scan is reported. Contrast-enhanced ultrasonography with perflubutane microbubbles and positron emission tomography-computed tomography (PET-CT) with 18F-fluorodeoxy glucose (FDG) in addition to dynamic CT were effective and useful for preoperative assessment of this patient. The pathological subtype of RCC in this patient was acquired cystic disease-associated RCC (ACD-associated RCC), which has been newly defined by Tickoo et al. (Am J Surg Pathol 30:141-153, 2006).

Heterotopic gastric mucosa in the gallbladder: report of two cases.

This report presents two cases of heterotopic gastric mucosa in the gallbladder. In case 1, the patient was a 43-year-old man who presented with diarrhea and fever. Abdominal ultrasonography showed a sessile polypoid lesion in the body of the gallbladder that grew over 2 months. Gallbladder carcinoma was suspected and a cholecystectomy was performed. Examination of an intraoperative frozen specimen of the elevated lesion in the body of the gallbladder suggested a gallbladder carcinoma invading the subserosal layer. A bile duct resection and regional lymph node dissection were performed. However, the postoperative permanent sections revealed heterotopic gastric mucosa in the gallbladder. Case 2 was an 80-year-old man. Screening abdominal ultrasonography revealed a sessile polypoid lesion in the gallbladder. This lesion was correctly diagnosed as heterotopic gastric mucosa in the gallbladder by the intraoperative frozen examination. The pertinent literature on this topic is reviewed.

Long-term natural history of acquired cystic disease of the kidney.

Patients with acquired cystic disease of the kidney (ACDK) were followed longitudinally over an average of 21.7 +/- 5.4 years to determine the natural history of the disease; that is, how big the kidneys become, when the kidney size reaches a plateau, and when the size regresses. Twenty-seven male and 20 female patients with chronic glomerulonephritis treated at our hospital were investigated. CT scans were performed once a year and kidney volume was measured. Two different quadratic curves with a node of 5.2 years for males and 2.5 years for females after the start of hemodialysis were fitted to log-transformed kidney volume to the duration of hemodialysis using a linear mixed model. The maximum kidney volume in male patients was obtained 21.1 years after the start of hemodialysis using this model. Peak values of kidney volume were demonstrated in 19 of 26 cases during the observation period. The median peak value (interquartile range) of bilateral kidney volumes was 274 (165-849) mL/1.73 m(2) occurring 19.1 +/- 4.5 years after the start of dialysis. In one male patient who had undergone nephrectomy due to renal cell carcinoma and in two of the remaining 26 male patients, the maximum kidney volume of 782 (residual kidney), 1151, and 1129 mL regressed to 428, 616, and 847 mL (reduction rate: 45.3, 46.5, and 25.0%) at 20.6, 25.4, and 23.1 years after the start of hemodialysis, respectively. Kidney enlargement due to ACDK reached a plateau after 21.1 years of hemodialysis in the male patients. Partial regression of severe ACDK may occur naturally after long-term hemodialysis without renal transplantation.

Activation of Holliday junction recognizing protein involved in the chromosomal stability and immortality of cancer cells.

We identified a novel gene HJURP (Holliday junction-recognizing protein) whose activation seemed to play a pivotal role in the immortality of cancer cells. HJURP was considered a possible downstream target for ataxia telangiectasia mutated signaling, and its expression was increased by DNA double-strand breaks (DSB). HJURP was involved in the homologous recombination pathway in the DSB repair process through interaction with hMSH5 and NBS1, which is a part of the MRN protein complex. HJURP formed nuclear foci in cells at S phase and those subjected to DNA damage. In vitro assays implied that HJURP bound directly to the Holliday junction and rDNA arrays. Treatment of cancer cells with small interfering RNA (siRNA) against HJURP caused abnormal chromosomal fusions and led to genomic instability and senescence. In addition, HJURP overexpression was observed in a majority of lung cancers and was associated with poor prognosis as well. We suggest that HJURP is an indispensable factor for chromosomal stability in immortalized cancer cells and is a potential novel therapeutic target for the development of anticancer drugs.

Phosphorylation and activation of cell division cycle associated 8 by aurora kinase B plays a significant role in human lung carcinogenesis.

Through genome-wide gene expression analysis of lung carcinomas, we detected in the great majority of lung cancer samples cotransactivation of cell division cycle associated 8 (CDCA8) and aurora kinase B (AURKB), which were considered to be components of the vertebrate chromosomal passenger complex. Immunohistochemical analysis of lung cancer tissue microarrays showed that overexpression of CDCA8 and AURKB was significantly associated with poor prognosis of lung cancer patients. AURKB directly phosphorylated CDCA8 at Ser(154), Ser(219), Ser(275), and Thr(278) and seemed to stabilize CDCA8 protein in cancer cells. Suppression of CDCA8 expression with small interfering RNA against CDCA8 significantly suppressed the growth of lung cancer cells. In addition, functional inhibition of interaction between CDCA8 and AURKB by a cell-permeable peptide corresponding to 20-amino acid sequence of a part of CDCA8 (11R-CDCA8(261-280)), which included two phosphorylation sites by AURKB, significantly reduced phosphorylation of CDCA8 and resulted in growth suppression of lung cancer cells. Our data imply that selective suppression of the CDCA8-AURKB pathway could be a promising therapeutic strategy for treatment of lung cancer patients.

Dikkopf-1 as a novel serologic and prognostic biomarker for lung and esophageal carcinomas.

Gene expression profile analysis of lung and esophageal carcinomas revealed that Dikkopf-1 (DKK1) was highly transactivated in the great majority of lung cancers and esophageal squamous cell carcinomas (ESCC). Immunohistochemical staining using tumor tissue microarrays consisting of 279 archived non-small cell lung cancers (NSCLC) and 280 ESCC specimens showed that a high level of DKK1 expression was associated with poor prognosis of patients with NSCLC as well as ESCC, and multivariate analysis confirmed its independent prognostic value for NSCLC. In addition, we identified that exogenous expression of DKK1 increased the migratory activity of mammalian cells, suggesting that DKK1 may play a significant role in progression of human cancer. We established an ELISA system to measure serum levels of DKK1 and found that serum DKK1 levels were significantly higher in lung and esophageal cancer patients than in healthy controls. The proportion of the DKK1-positive cases was 126 of 180 (70.0%) NSCLC, 59 of 85 (69.4%) SCLC, and 51 of 81 (63.0%) ESCC patients, whereas only 10 of 207 (4.8%) healthy volunteers were falsely diagnosed as positive. A combined ELISA assays for both DKK1 and carcinoembryonic antigen increased sensitivity and classified 82.2% of the NSCLC patients as positive whereas only 7.7% of healthy volunteers were falsely diagnosed to be positive. The use of both DKK1 and ProGRP increased sensitivity to detect SCLCs up to 89.4%, whereas false-positive rate in healthy donors was only 6.3%. Our data imply that DKK1 should be useful as a novel diagnostic/prognostic biomarker in clinic and probably as a therapeutic target for lung and esophageal cancer.

Identification of Myc-associated protein with JmjC domain as a novel therapeutic target oncogene for lung cancer.

Through genome-wide expression profile analysis for non-small cell lung cancers (NSCLC), we found overexpression of a Myc-associated protein with JmjC domain (MAPJD) gene in the great majority of NSCLC cases. Induction of exogenous expression of MAPJD into NIH3T3 cells conferred growth-promoting activity. Concordantly, in vitro suppression of MAPJD expression with small interfering RNA effectively suppressed growth of NSCLC cells, in which MAPJD was overexpressed. We found four candidate MAPJD target genes, SBNO1, TGFBRAP1, RIOK1, and RASGEF1A, which were the most significantly induced by exogenous MAPJD expression. Through interaction with MYC protein, MAPJD transactivates a set of genes, including kinases and cell signal transducers that are possibly related to proliferation of lung cancer cells. As our data imply that MAPJD is a novel member of the MYC transcriptional complex and its activation is a common feature of lung cancer, selective suppression of this pathway could be a promising therapeutic target for treatment of lung cancers.

Increased expression of insulin-like growth factor-II messenger RNA-binding protein 1 is associated with tumor progression in patients with lung cancer.

PURPOSE: To identify novel biomarkers and therapeutic targets for lung cancers, we screened for genes that were highly transactivated in a large proportion of non-small cell lung cancers (NSCLC) using a cDNA microarray representing 27,648 genes. EXPERIMENTAL DESIGN: A gene encoding insulin-like growth factor-II mRNA-binding protein 1 (IMP-1) was selected as a candidate (> or =3-fold expression than in normal lung tissue in about 70% of NSCLCs). Tumor tissue microarray was applied to examine expression of IMP-1 protein in archival lung cancer samples from 267 patients and investigated its clinicopathologic significance. A role of IMP-1 in cancer cell growth and/or survival was examined by small interfering RNA experiments. Cellular invasive activity of IMP-1 on mammalian cells was examined using Matrigel assays. mRNAs associated with IMP-1 in cancer cells were also isolated by RNA immunoprecipitation followed by cDNA microarray analysis. RESULTS: Positive immunostaining of IMP-1 was correlated with male (P = 0.0001), tumor size (P = 0.0003), non-adenocarcinoma histology (P < 0.0001), smoking history (P = 0.0005), non-well-differentiated tumor grade (P = 0.0001), and poor prognosis (P = 0.0053). Suppression of IMP-1 expression with small interfering RNA effectively suppressed growth of NSCLC cells. In addition, we identified that exogenous expression of IMP-1 increased the migratory activity of mammalian cells. IMP-1 was able to bind to mRNAs encoding a variety of proteins involved in signal transduction, cell cycle progression, cell adhesion and cytoskeleton, and various types of enzymatic activities. CONCLUSIONS: These results suggest that IMP-1 expression is likely to play important roles in lung cancer development and progression, and that IMP-1 is a prognostic biomarker and a promising therapeutic target for lung cancer.

Activation of CDCA1-KNTC2, members of centromere protein complex, involved in pulmonary carcinogenesis.

We found cotransactivation of cell division associated 1 (CDCA1) and kinetochore associated 2 (KNTC2), members of the evolutionarily conserved centromere protein complex, in non-small cell lung carcinomas (NSCLC). Immunohistochemical analysis using lung cancer tissue microarray confirmed high levels of CDCA1 and KNTC2 proteins in the great majority of lung cancers of various histologic types. Their elevated expressions were associated with poorer prognosis of NSCLC patients. Knockdown of either CDCA1 or KNTC2 expression with small interfering RNA significantly suppressed growth of NSCLC cells. Furthermore, inhibition of their binding by a cell-permeable peptide carrying the CDCA1-derived 19-amino-acid peptide (11R-CDCA1(398-416)) that correspond to the binding domain to KNTC2 effectively suppressed growth of NSCLC cells. As our data imply that human CDCA1 and KNTC2 seem to fall in the category of cancer-testis antigens, and that their simultaneous up-regulation is a frequent and important feature of cell growth/survival of lung cancer, selective suppression of CDCA1 or KNTC2 activity and/or inhibition of the CDCA1-KNTC2 complex formation could be a promising therapeutic target for treatment of lung cancers.

The neuromedin U-growth hormone secretagogue receptor 1b/neurotensin receptor 1 oncogenic signaling pathway as a therapeutic target for lung cancer.

Using a genome-wide cDNA microarray to search for genes that were specifically up-regulated in non-small cell lung cancers (NSCLC), we identified an abundant expression of neuromedin U (NMU) in the great majority of lung cancers. Immunohistochemical analysis showed a significant association of NMU expression with poorer prognosis of patients with NSCLC. Treatment of NSCLC cells with short interfering RNA against NMU suppressed its expression and inhibited the growth of the cells; on the other hand, the induction of exogenous expression of NMU conferred growth-promoting activity and enhanced cell mobility in vitro. We found that two G protein-coupled receptors, growth hormone secretagogue receptor 1b and neurotensin receptor 1, were also overexpressed in NSCLC cells, and that a heterodimer complex of these receptors functioned as an NMU receptor. The NMU-receptor interaction subsequently induced the generation of a second messenger, cyclic AMP, to activate its downstream genes including transcription factors and cell cycle regulators. Treatment of NSCLC cells with short interfering RNAs for growth hormone secretagogue receptor or neurotensin receptor 1 suppressed the expression of those genes and the growth of NSCLC cells. These data strongly implied that targeting the NMU signaling pathway would be a promising therapeutic strategy for the treatment of lung cancers.

Proteomic analysis of serum, outflow dialysate and adsorbed protein onto dialysis membranes (polysulfone and pmma) during hemodialysis treatment using SELDI-TOF-MS.

AIMS: Alterations in the profiling of peptides and proteins in the serum, outflow dialysate and adsorbed protein on the dialysis membrane were investigated. METHODS: Alterations in the protein profiling of routine hemodialysis using polysulfone (TS-UL) and PMMA (moderate flux membrane of polymethylmethacrylate: BK-U) in 8 patients and that of adsorption onto polysulfone and PMMA membranes in 4 patients were evaluated by SELDI-TOF-MS and ProteinChip array. Mass-to-charge ratios (m/z) between 2,000 and 120,000 were analyzed. RESULTS: The protein with a relative intensity of m/z 11,730 measured by SELDI-TOF-MS was present in a small amount in the outflow dialysate and in a large amount in adsorption (identified as beta2-microglobulin) onto PMMA membrane. Unexpectedly, 68 molecular masses of peptides that were adsorbed more onto polysulfone than onto PMMA membrane were observed. There were more peptides less than m/z 11,730 adsorbed onto polysulfone membrane than onto PMMA membrane. Dominant peaks, m/z 6,629 and 6,431 adsorbed onto polysulfone membrane were identified as apolipoprotein CI and truncated apolipoprotein CI, respectively. 37 proteins with molecular weights larger than m/z 11,730 showed greater filtration through PMMA membrane than through polysulfone membrane. 149 molecular masses that were adsorbed onto PMMA or more onto PMMA membrane than onto polysulfone membrane were observed. CONCLUSION: This experiment suggests that membrane adsorption is an important mechanism for the removal of middle-molecular-weight proteins by hemodialysis using not only PMMA membrane but also polysulfone membrane. Adsorption of peptide or protein onto a dialysis membrane may depend not only on the membrane material, but also on the peptide or protein.