Configurationally Nonselective Aquation of a Mononuclear Ru(II) Chloro Complex to Aquo Complex Isomers with Distinctive Aspects in Photoisomerization, Redox, and Catalytic Water Oxidation.

distal-[Ru(EtOtpy)(pynp)Cl]+ (d-EtO1Cl) (EtOtpy = 4'-ethoxy-2,2':6',2″-terpyridine, pynp = 2-(2-pyridyl)-1,8-naphthyridine), and distal/proximal-[Ru(EtOtpy)(pynp)OH2]2+ (d/p-EtO1H2O) complexes were newly synthesized to investigate the synergistic influence of the geometric configuration coupled with substituent introduction of an ethoxy (EtO) group on the physicochemical properties and reactions of the Ru(II) complexes. Configurationally nonselective aquation of d-EtO1Cl was uniquely observed to form d/p-EtO1H2O isomers in water, in contrast to configurationally selective aquation of distal-[Ru(tpy)(pynp)Cl]+ (d-1Cl, tpy = 2,2':6',2″-terpyridine) without the EtO group [Yamazaki, H. . J. Am. Chem. Soc. 2011, 133, 8846-8849].The kinetic profiles of the aquation reactions of d-EtO1Cl were well analyzed using a sequential reversible reaction model assuming the reversible interconversion between d/p-EtO1H2O isomers via d-EtO1Cl. The observed equilibrium constant (Kiso) of isomerization between p/d-EtO1H2O was calculated from the kinetic analysis as Kiso = 0.45, which is consistent with the final concentration ratio (1:0.43) of p/d-EtO1H2O generated in the aquation reaction of d-EtO1Cl. The irreversible photoisomerization from d-EtO1H2O to p-EtO1H2O was observed in water with an internal quantum yield (Φ) of 0.44% at 520 nm. Electrochemical measurements showed that d-EtO1H2O undergoes a 2-step oxidation reaction of 1H+-coupled 1e- processes of RuII-OH2/RuIII-OH and RuIII-OH/RuIV═O at pH 1.3-9.7, whereas p-EtO1H2O undergoes a 1-step oxidation reaction of a 2H+-coupled 2e- process of RuII-OH2/RuIV═O in the pH range of 1.8-11.5. Any redox potential of d/p-EtO1H2O isomers was decreased by the electro-donating EtO substitution, compared with distal/proximal-[Ru(tpy)(pynp)OH2]2+ (d/p-1H2O). The turnover frequency (kO2 = 1.7 × 10-2 s-1) of d-EtO1H2O for water oxidation catalysis is higher than that (3.5 × 10-4 s-1) of p-EtO1H2O by a factor of 48.6. The kO2 value (1.7 × 10-2 s-1) for d-EtO1H2O is 4.5-fold higher than those of d-1H2O (3.8 × 10-3 s-1). The higher kO2 value of d-EtO1H2O compared with d-1H2O could be explained by the fast oxidation rate from RuIV═O to RuV═O involved in the rate-determining step due to the electron-donating EtO group.

Distinctive Aspects in Aquation, Proton-Coupled Redox, and Photoisomerization Reactions between Geometric Isomers of Mononuclear Ruthenium Complexes with a Large-π-Conjugated Tetradentate Ligand.

Geometric isomers of mononuclear ruthenium(II) complexes, distal-/proximal-[Ru(tpy)(dpda)Cl]+ (d-/p-RuCl, tpy = 2,2':6',2″-terpyridine, dpda = 2,7-bis(2-pyridyl)-1,8-diazaanthracene), were newly synthesized to comprehensively investigate the geometric and electronic structures and distinctive aspects in various reactions between isomers. The ultraviolet (UV)-visible absorption spectra of d-/p-RuCl isomers show intense bands for metal-to-ligand charge transfer (MLCT) at close wavelengths of 576 and 573 nm, respectively. However, time-dependent density functional theory (TD-DFT) calculations suggest that the MLCT transition of d-RuCl involves mainly single transitions to the π* orbital of the dpda ligand in contrast to mixing of the π* orbitals of the dpda and tpy ligands for p-RuCl. The aquation reaction (1.5 × 10-3 s-1) of p-RuCl to yield proximal-[Ru(tpy)(dpda)(OH2)]2+ (p-RuH2O) is faster than that (5.3 × 10-6 s-1) of d-RuCl in D2O/CD3OD (4:1 v/v) by three orders of magnitude, which resulted from the longer Ru-Cl bond by 0.017 Å and the distorted angle (100.2(3)°) of Cl-Ru-N (a nitrogen of dpda, being on a tpy plane) due to the steric repulsion between Cl and dpda for p-RuCl. Electrochemical measurements showed that d-RuH2O undergoes a 2-step oxidation reaction of 1H+-coupled 1e- processes of RuII-OH2/RuIII-OH and RuIII-OH/RuIV═O at pH 1-9, whereas p-RuH2O undergoes a 1-step oxidation reaction of a 2H+-coupled 2e- process of RuII-OH2/RuIV═O in the pH range of pH 1-10. The irreversible photoisomerization from d-RuH2O to p-RuH2O was observed in aqueous solution with an internal quantum yield (Φ) of 5.4 × 10-3% at 520 nm, which is lower compared with Φ = 1.1-2.1% of mononuclear Ru(II) aquo complexes with similar bidentate ligands instead of dpda by three orders of magnitude. This is possibly ascribed to the faster nonradiative decay rate from the excited 3MLCT state to the ground state for d-RuH2O due to the lower π* level of dpda ligands according to the energy-gap law: the rate decreases exponentially with the increasing energy gap.

Pancreatic metastases of cerebellar hemangiopericytoma occurring 24 years after initial presentation: report of a case.

Hemangiopericytoma (HPC) preferentially developing in soft tissues and the meninges has been gradually recognized to be an aggressive, highly metastatic tumor. We herein report the case of a 65-year-old male with pancreatic metastases of cerebellar HPC that developed following two resections of intracranial local recurrent foci, 24 years after the initial craniotomy and 7 years after resection of metastases to the lungs and kidneys. Follow-up abdominal computed tomography scanning and magnetic resonance imaging revealed a solitary tumor in the pancreatic body. Since no other recurrent foci were detectable, distal pancreatectomy was performed. Another metastasis was incidentally found in the resected pancreas. Both foci were pathologically proven to be metastases of HPC. Among the 12 reported cases of pancreatic metastases of HPC, including ours, this case showed the longest duration between initial onset and the development of pancreatic metastases, suggesting that providing long-term follow-up is necessary for HPC patients.

Detection of intrahepatic veno-venous shunts by three-dimensional venography using multidetector-row computed tomography during angiography.

PURPOSE: The hepatic vein (HV) can be removed during hepatectomy if there is an effective intrahepatic veno-venous shunt (vv-shunt). We evaluated the efficacy of vv-shunt detection by three-dimensional (3D) venography reconstructed from multidetector-row computed tomography (MDCT) during angiography. METHODS: 3D venography was reconstructed using computer software in 88 patients with intrahepatic tumors. RESULTS: We found that 12 patients had one shunt [4 right hepatic vein (RHV)-middle hepatic vein (MHV) and 12 RHV- inferior right hepatic vein (IRHV)] and 1 patient had 2 shunts (RHV-MHV and -IRHV), confirming a clinically efficient vv-shunt in 14.8% of the patients. In one patient with an RHV-IRHV shunt, the preserved RHV-IRHV shunt worked well and prevented congestion of the postero-caudal subsegment after central bisegmentectomy with partial resection of the RHV ventral trunk for huge hepatocellular carcinoma (HCC). CONCLUSIONS: Although the vv-shunt detection rate by 3D venography is low, a visualized vv-shunt proved to be efficient. Thus, invasive occlusion venography is avoidable if a vv-shunt is seen on 3D venography.

Usefulness of Palliative Prognostic Index, Objective Prognostic Score, and Neutrophil-Lymphocyte Ratio/Albumin Ratio As Prognostic Indicators for Patients Without Cancer Receiving Home-Visit Palliative Care: A Pilot Study at a Community General Hospital.

Background: Although the palliative prognostic index (PPI), objective prognostic score (OPS), and neutrophil-lymphocyte ratio/albumin ratio (NLR/Alb) are well-known prognostic indicators for cancer patients, they do not provide clarity when it comes to predicting prognosis in patients without cancer who receive home-visit palliative care. Objective: The aim of this study was to determine whether PPI, OPS, and NLR/Alb can predict prognosis for patients without cancer who received home-visit palliative care. Design: This is a retrospective study. Setting/Subjects: We recruited 58 patients without cancer who received home-visit palliative care from Tokushima Prefectural Kaifu Hospital, Japan, and died at home or at the hospital within seven days of admission between January 2009 and March 2023. Measurements: The PPI, OPS, and NLR/Alb of the study patients were evaluated at regular intervals, and statistical analysis was performed on the relationship between these indices and the time to death. Results: Simple regression analysis showed that PPI, OPS, and NLR/Alb were negatively correlated with the period until death (p < 0.001). The survival curves of the groups classified according to PPI, OPS, and NLR/Alb were significantly stratified. The predictive capacities of PPI, OPS, and NLR/Alb for death within 21 days were as follows: PPI (area under the curve [AUC]: 0.71; sensitivity: 59%; specificity: 68%), OPS (AUC: 0.73; sensitivity: 88%; specificity: 47%), and NLR/Alb (AUC: 0.72; sensitivity: 72%; specificity: 73%). Conclusions: PPI, OPS, and NLR/Alb were useful in predicting the survival period and short-term prognosis within 21 days for patients without cancer who received home-visit palliative care.

Lysophosphatidylcholine acyltransferase 1 altered phospholipid composition and regulated hepatoma progression.

BACKGROUND & AIMS: Several lipid synthesis pathways play important roles in the development and progression of hepatocellular carcinoma (HCC), although the precise molecular mechanisms remain to be elucidated. Here, we show the relationship between HCC progression and alteration of phospholipid composition regulated by lysophosphatidylcholine acyltransferase (LPCAT). METHODS: Molecular lipidomic screening was performed by imaging mass spectrometry (IMS) in 37 resected HCC specimens. RT-PCR and Western blotting were carried out to examine the mRNA and protein levels of LPCATs, which catalyze the conversion of lysophosphatidylcholine (LPC) into phosphatidylcholine (PC) and have substrate specificity for some kinds of fatty acids. We examined the effect of LPCAT1 overexpression or knockdown on cell proliferation, migration, and invasion in HCC cell lines. RESULTS: IMS revealed the increase of PC species with palmitoleic acid or oleic acid at the sn-2-position and the reduction of LPC with palmitic acid at the sn-1-position in HCC tissues. mRNA and protein of LPCAT1, responsible for LPC to PC conversion, were more abundant in HCCs than in the surrounding parenchyma. In cell line experiments, LPCAT1 overexpression enriched PCs observed in IMS and promoted cell proliferation, migration, and invasion. LPCAT1 knockdown did viceversa. CONCLUSIONS: Enrichment or depletion of some specific PCs, was found in HCC by IMS. Alteration of phospholipid composition in HCC would affect tumor character. LPCAT1 modulates phospholipid composition to create favorable conditions to HCC cells. LPCAT1 is a potent target molecule to inhibit HCC progression.

Detection of hepatocellular carcinomas with near-infrared fluorescence imaging using indocyanine green: its usefulness and limitation.

BACKGROUND: Indocyanine green (ICG), an agent for measuring liver function, becomes fluorescent under near-infrared (NIR) light after binding to serum proteins. Hepatocellular carcinoma (HCC) with a deposit of preoperatively administered ICG becomes clearly detectable under ICG fluorography; however, it remains unclear whether this detection method is always reliable. This case series study was designed to clarify the reliability of this method. METHODS: ICG (0.5 mg/kg) was injected from the 3rd to 28th preoperative day to evaluate hepatic function in 58 patients with HCCs. Preoperative imaging modalities identified 76 HCC foci. The operative fields and resected specimens were observed with an NIR camera system. Preoperatively detected lesions and lesions newly detected by the ICG fluorography were histologically investigated. RESULTS: ICG fluorography identified 73 of 76 preoperatively diagnosed HCC lesions. Intraoperative ICG fluorography visualized 47 lesions in 40 patients. The other 26 lesions showing emission were found in the sectioned specimens under NIR observation. Other than preoperatively diagnosed foci, ICG fluorography visualized 35 new lesions, including 6 HCCs, 2 dysplastic nodules and 27 non-neoplastic lesions, such as bile plugs and cysts. The sensitivity of ICG fluorography for HCCs was 96% and its positive predictive value was 71.5%. CONCLUSIONS: Indocyanine green fluorography is useful to detect HCCs; however, attention should be paid to the fact that HCCs may be occasionally overlooked by this imaging method and that lesions detected by this method are not always neoplastic lesions.

Anomalous arterial ramification in the right liver.

PURPOSE: The aim of this study was to investigate whether individual arterial and portal venous division during hepatectomy is always safe by examining the presence of the anomalous arterial ramification in the right liver. METHODS: The ramifications of the right hepatic artery (RHA) were investigated by three-dimensional (3D) reconstruction imaging using a computer software program in 87 patients undergoing computed tomography during angiography as a preoperative assessment of intrahepatic tumors. RESULTS: The anterior view showed that the RHA bifurcated into the anterior and posterior sector arteries at the hilum in 76 patients. Sector-intersecting arteries from the posterior to the anterior sector and vice versa were found in 7 and 4 of those patients, respectively. The RHA in the other 11 patients was divided in a complex manner into more than 2 arteries: e.g., the first branch to the cranial part of the posterior sector, the second to the anterior sector, and the third to the caudal part of the posterior sector. A total of 22 patients showed anomalous ramification of RHA. CONCLUSION: Preoperative observation of the hepatic artery by 3D imaging is very useful to detect anomalous ramification. Arterial dissection during the intrafascial approach should be cautiously performed based on the 3D images.

Comparison of therapeutic responses between polymyalgia rheumatica and remitting seronegative symmetrical synovitis with pitting edema syndrome.

Polymyalgia rheumatica (PMR) and remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome are common inflammatory rheumatic diseases in the elderly. In this study, we investigated the difference of the therapeutic responses between patients with PMR and RS3PE syndrome. Twenty-four patients with PMR and 12 patients with RS3PE syndrome were treated with initial dosages of 10-20 mg per day oral prednisolone, and the dosages were then tapered. Percentages of patients with negative c-reactive protein (CRP) after 8-week treatment were significantly more in RS3PE syndrome than in PMR. Percentages of patients with relapse during one-year treatment were less likely to be in RS3PE syndrome than in PMR. These differences observed between the two disorders were not associated with the level of initial CRP. There was no significant difference in percentages of patients with prednisolone-free remission after two-year treatment between PMR and RS3PE syndrome. These results indicate that the early response to the treatment is greater in RS3PE syndrome than in PMR. J. Med. Invest. 70 : 145-149, February, 2023.

Impact of cell cycle disruption on impaired hepatic regeneration in aged livers with ischemic insult.

BACKGROUND: The number of elderly patients with hepatobiliary malignancies has increased with the steady growth of elderly population. However, the safety of major hepatectomy for elderly patients remains controversial. This study investigated the effect of aging on the hepatic regenerative response after partial resection of livers subjected to ischemic insult. METHODS: Two-thirds hepatectomy following 1-h hepatic ischemia was performed in young (12-wk-old) and old (18-mo-old) rats under portosystemic shunt establishment by subcutaneous transposition of the spleen. RESULTS: The survival rate 48 h after hepatectomy of the old rats was significantly lower (20%) than that of the young rats (53%), whereas all animals without hepatic ischemia were alive at 48 h. Hepatic necrosis and hepatocyte apoptosis during the early post-hepatectomy phase were more severe in the aged livers, which also showed delayed Akt activation. Liver mass restoration was significantly retarded in the old rats, despite higher plasma IL-6 levels, rapid and prolonged activation of hepatic STAT3, and increased hepatocyte nuclear cyclin D1 levels. In the young livers, cyclin E, which is essential for G1/S transition, and cyclin A, a marker of S phase, were observed in the nucleus from 24 h, reaching peaks 48 h after hepatectomy. In contrast, the old livers showed greatly delayed and decreased nuclear cyclin E and cyclin A levels. CONCLUSION: Age-related reductions in the regenerative ability of ischemically damaged livers may be caused by cell cycle disruption at either the late G1 phase or the G1/S transition, despite increased cyclin D1 levels and compensatory IL-6/STAT3 activation.

Peripancreatic arterial anatomy analyzed by 3-dimensional multidetector-row computed tomography.

BACKGROUND/AIMS: Since the anatomy of the peripancreatic vessel system is complex, it is important to preoperatively clarify the running aspects of such vessels, especially when pancreatoduodenectomy is performed. METHODOLOGY: In 166 patients undergoing multidetector-row computed tomography, peripancreatic vessels were three-dimensionally reconstructed using computer software. RESULTS: The dorsal pancreatic artery branched from the splenic artery (45.4%), common hepatic artery (24.8%), superior mesenteric artery (SMA, 15.6%), celiac axis (9.9%) and other arteries such as the middle colic artery (4.3%). Branching of the inferior pancreatoduodenal artery (IPDA) was categorized into two types: a single main IPDA branching from one artery, such as the first jejunal artery (J1a, 55.2%) and SMA (25.1%) and two IPDAs branching from one artery (J1a, 7.0% or SMA, 2.8%) or separately from two arteries (3.5%). Most IPDAs (129 of identified 168 IPDAs) ran behind the SMA at the right edge of the SMA. In 52 patients, superior mesenteric vein tributaries ran above the SMA and mask the IPDA's ramification. CONCLUSIONS: Peripancreatic vessel anatomy is very complex. The preoperative 3D arteriography and portography enables us to obtain precise information about peripancreatic vessels.

[Impact on opioid precipitation of opioid-starting titration path].

To investigate the effect clinical path of cancer pain treatments for opioid naive patients has on physician practice, a prepost quasi-experimental study was performed. The primary outcome measure was the percentage of patients who received 'recommended pain treatments' during the study periods. We determined the treatment to be the treatment of choice, if the physician 1) ordered a rescue dose, 2) prescribed a laxative, and 3) prescribed antiemetics when starting opioids. The secondary outcome measure was the number of newly consulted patients for our palliative care team. The end-points were measured before and after disseminating the clinical path. The rate of patients receiving recommended pain treatments significantly increased after disseminating the clinical path(p=0.03): 17%(33/18)to 61%(19/31). Patients who received a rescue order, laxative, or antiemetic when starting opioids were: 44% vs. 68%, 77% vs. 90%, and 66% vs. 77%, respectively. The number of patients newly consulting the palliative care team was increased(21 cases to 42 cases/4 month). In conclusion, the clinical path of cancer pain treatments is useful for improving the physician's practice when starting opioids for cancer pain, and might contribute to enhancing palliative care team availability.

Hepatectomy for metastatic liver tumors complicated with right umbilical portion.

We report the case of a 76-year-old man, presenting with a right umbilical portion (RUP), with two liver metastases of rectal cancer, 2cm and 1 cm tumors in the caudate lobe and anterior segment, respectively. The portal first branch ran to the right posterior segment and the remaining formed a left trunk, thereafter forming RUP. The tumor in the caudate was close to the right posterior segment's Glissonean pedicle. On 3-dimensional CT analysis under tubography via an endoscopic naso-biliary tube, the anatomical patterns of the arteries and bile ducts were complicated. On laparotomy, the gallbladder was located to the left of the round ligament. Right posterior segmentectomy plus partial caudate resection and partial hepatectomy of the anterior segment was performed after skeletonization of the biliovascular structures at the hepatic hilum. Precise examination of the biliovascular structures is needed to safely perform hepatectomy in patients complicated with RUP.

Postoperative bile leakage managed by interventional intrabiliary ethanol ablation.

We report a case of postoperative bile leakage that was successfully managed by intrabiliary ethanol ablation. A 68-year-old man with peritoneal and liver metastases from a jejunal gastrointestinal stromal tumor (GIST), which were refractory to molecular-targeted agents, underwent extended left lobectomy and peritoneal tumor resection. Bile leakage from the drainage tube persisted at a constant volume of 100 ml per day. On the 20th postoperative day, fistulography through a drainage tube and endoscopic cholangiography revealed biliary leakage from the bile ducts of segments 5 and 1. Since these bile ducts did not communicate with the proximal hilar bile ducts, two 5F balloon catheters were separately advanced into the leaking bile ducts via the drainage tube on day 30, and 1 ml absolute ethanol was injected into both of these catheters for 10 minutes. After three sessions of ethanol ablation, the bile leakage stopped. Although the bile leakage from segment 1 relapsed five days later, it gradually decreased and then stopped again until day 70. Intrabiliary ethanol ablation using the interventional technique is useful for managing bile leakage after hepatectomy when the leaking distal bile duct is isolated from the proximal biliary tree.

[A case of hilar bile duct cancer which recurred at abdominal and cervical lymph nodes 8 years after curative resection].

A 40-year-old man underwent right hemihepatectomy with biliary reconstruction for hilar bile duct cancer, and the surgical margin being negative. The tumor, showing atypical intraductal growth, was solid adenocarcinoma with rich mucinous component, although it was negative for MUC1, MUC2 and MUC5AC, suggesting that the tumor was not an intraductal papillary neoplasm of the bile duct (IPN-B). Eight years after operation, abdominal and cervical lymph node metastases were found on computed tomography and (18)F-deoxyglucose positron emission tomography examination. Late remote recurrence after curative resection of the extrahepatic bile duct cancer is relatively rare. The recurrence in the present case maybe explained by the tumor dormancy theory.

[Primary hepatic actinomycosis concomitant with elevation of protein induced by vitamin K absence or antagonist II - report of a case].

We report a case of primary hepatic actinomycosis showing elevation of serum protein induced by vitamin K absence or antagonist II (PIVKA-II). A 68-year-old man visited an affiliated hospital with a complaint of high fever and body weight loss. Hematological examination revealed severe inflammatory reactions and liver dysfunction. Abdominal CT showed a heterogeneous low density area composed of cystic and solid part. We suspected the cystic part with band-like enhancement to be a hepatic abscess and performed percutaneous transhepatic abscess drainage. Although inflammatory reactions decreased after the drainage, the solid part did not shrink and blood chemistry revealed elevation of PIVKA-II. Since we could not rule out the possibility of hepatoma, right hepatectomy was performed. Histological examination revealed actinomycetes. Although primary hepatic actinomycosis is a rare disease, it must be kept in mind in the differential diagnosis of the liver tumor.

Mass spectrometric profiling of DNA adducts in the human stomach associated with damage from environmental factors.

BACKGROUND: A comprehensive understanding of DNA adducts, one of the most plausible origins of cancer mutations, is still elusive, especially in human tissues in clinical settings. Recent technological developments have facilitated the identification of multiple DNA adducts in a single experiment. Only a few attempts toward this "DNA adductome approach" in human tissues have been reported. Geospatial information on DNA adducts in human organs has been scarce. AIM: Mass spectrometry of human gastric mucosal DNA was performed to identify DNA adducts associated with environmental factors. MATERIALS AND METHODS: From 59 subjects who had received gastrectomy for gastric cancer, 306 samples of nontumor tissues and 15 samples of tumors (14 cases) were taken for DNA adductome analysis. Gastric nontumor tissue from autopsies of 7 subjects without gastric cancer (urothelial cancer, hepatocellular carcinoma, lung cancer each; the other four cases were without any cancers) was also investigated. Briefly, DNA was extracted from each sample with antioxidants, digested into nucleosides, separated by liquid chromatography, and then electrospray-ionized. Specific DNA adducts were identified by mass/charge number and column retention time compared to standards. Information on lifestyle factors such as tobacco smoking and alcohol drinking was taken from the clinical records of each subject. RESULTS: Seven DNA adducts, including modified bases, C5-methyl-2'-deoxycytidine, 2'-deoxyinosine, C5-hydroxymethyl-2'-deoxycytidine, N6-methyl-2'-deoxyadenosine, 1,N6-etheno-2'-deoxyadenosine, N6-hydroxymethyl-2'-deoxyadenosine, and C8-oxo-2'-deoxyguanosine, were identified in the human stomach and characterized. Intraindividual differences according to the multiple sites of these adducts were noted but were less substantial than interindividual differences. N6-hydroxymethyl-2'-deoxyadenosine was identified in the human stomach for the first time. The amount of C5-hydroxymethyl-2'-deoxycytidine was higher in the stomachs of subjects without gastric cancer than in the nontumor and tumor portions of the stomach in gastric cancer patients. Higher levels of 1,N6-etheno-2'-deoxyadenosine were detected in the subjects who reported both smoking and drinking than in those without these habits. These DNA adducts showed considerable correlations with each other. CONCLUSIONS: We characterized 7 DNA adducts in the nontumor portion of the human stomach in both gastric cancer subjects and nongastric cancer subjects. A reduction in C5-hydroxymethyl-dC even in the nontumor mucosa of patients with gastric cancer was observed. Smoking and drinking habits significantly influenced the quantity of one of the lipid peroxidation-derived adducts, etheno-dA. A more expansive DNA adductome profile would provide a comprehensive understanding of the origin of human cancer in the future.

Geospatial Assessments of DNA Adducts in the Human Stomach: A Model of Field Cancerization.

BACKGROUND: Field cancerization is a popular concept regarding where cancer cells arise in a plane, such as the opened-up gastrointestinal mucosa. The geospatial distribution of DNA adducts, some of which are believed to initiate mutation, may be a clue to understanding the landscape of the preferred occurrence of gastric cancer in the human stomach, such that the occurrence is much more frequent in the lesser curvature than in the greater curvature. METHODS: Seven DNA adducts, C5-methyl-2'-deoxycytidine, 2'-deoxyinosine, C5-hydroxymethyl-2'-deoxycytidine, N6-methyl-2'-deoxyadenosine, 1,N6-etheno-2'-deoxyadenosine, N6-hydroxymethyl-2'-deoxyadenosine, and C8-oxo-2'-deoxyguanosine, from different points and zones of the human stomach were semi quantitatively measured by liquid chromatography/tandem mass spectrometry. The differences in the quantity of these DNA adducts from the lesser and greater curvature, the upper, middle and lower third zones, the anterior and posterior wall of the stomach, and the mucosae distant from and near the tumor were compared to determine whether the location preference of cancer in the stomach could be explained by the distribution of these DNA adducts. Comparisons were conducted considering the tumor locations and operation methods. CONCLUSIONS: Regarding the DNA adducts investigated, significant differences in quantities and locations in the whole stomach were not noted; thus, these DNA adducts do not explain the preferential occurrence of cancer in particular locations of the human stomach.

Pancreatic neuroendocrine cell tumor secreting parathyroid hormone-related protein and gastrin: Report of a case.

This report presents a case of pancreatic neuroendocrine cell carcinoma with multiple liver metastases secreting gastrin and parathyroid hormone-related protein (PTHrP) related to lumbar bone fracture and hypercalcemia. A 58-year-old woman visited an affiliated hospital with a chief complaint of lumbago without any evidence of trauma. She was diagnosed with hepatic dysfunction and hypercalcemia as well as multiple lumbar compression fractures without osteolytic lesions. Abdominal computed tomography (CT) showed a hypervascular mass in the pancreatic tail and multiple liver tumors. Duodenal ulcers were found with gastrointestinal endoscopy. There was a marked increase in the serum gastrin level. She was diagnosed as gastrinoma with multiple liver metastases and was admitted to the hospital. She had an increase in serum PTHrP level without the elevation of intact parathyroid hormone at the time of admission. She underwent an extended right hepatectomy in addition to a distal pancreatectomy with a regional lymphadenectomy and splenectomy. The postoperative course was uneventful, and serum gastrin and PTHrP activities reduced to normal levels. She remained symptom-free, and serum calcium, gastrin, and PTHrP levels remain within the normal ranges 19 months after surgery without adjuvant therapy.

Impact of the preoperative des-gamma-carboxy prothrombin level on prognosis after hepatectomy for hepatocellular carcinoma meeting the Milan criteria.

PURPOSE: Hepatectomy is feasible for patients with hepatocellular carcinoma (HCC) who are eligible for liver transplantation according to the Milan criteria if they have good hepatic function. This retrospective study investigates the prognostic factors of hepatectomy in HCC patients meeting the Milan criteria. METHODS: Between 1991 and 2005, 175 patients underwent hepatectomy for HCC at our institute; 111 met and 64 exceeded the Milan criteria. The prognostic factors for hepatectomy were investigated using a Cox regression model. RESULTS: Operative mortality and morbidity were significantly lower in the patients who met the criteria than in those who exceeded the criteria. After a median follow-up of 51.5 months, the 5-year survival rate was significantly better for the patients who met the criteria than for those who exceeded the criteria (77.8% vs 35.7%; P < 0.0001). The factors predictive of poor prognosis were poor differentiation, microscopic vasculobiliary invasion, and a high serum des-gamma-carboxy prothrombin (DCP) level (>100 mAU/ml) for the patients who met the Milan criteria; and only the presence of a microsatellite lesion for the patients who did not meet the Milan criteria. CONCLUSIONS: Hepatectomy is safe and beneficial for HCC patients who meet the Milan criteria, but a high preoperative serum DCP level may be predictive of a poor prognosis.