Colorectal resection by a minilaparotomy approach vs. conventional operation for colon cancer. Results of a prospective randomized trial.

BACKGROUND/AIMS: The aim of this study was to evaluate the outcome of patients undergoing colorectal resection for colon cancer using a minilaparotomy approach or conventional surgical procedure. METHODOLOGY: In a prospective randomized trial, twenty consecutive patients undergoing colon resection by minilaparotomy and 26 patients undergoing conventional open colorectal resection were evaluated. Immunologic, metabolic and hemodynamic studies were performed in all patients. Cell surface markers were used to characterize Th1/2 balance, using flow cytometry. Indirect calorimetry to measure energy expenditure, and pulse dye densitometry for a hemodynamic study were performed in patients until 14 POD. RESULTS: The lengths of laparotomy incisions were 7.5+/-1.5 cm and 20.5+/-2.5 cm in the minilaparotomy and conventional group, respectively. Mean operative time, morbidity and postoperative hospital stay of the two groups was not significantly different. However, mean operative blood loss, days to p.o. liquids and walking, and amount of analgesic usage were significantly less in the minilaparotomy group. The postoperative ratio of Th1/2 in CD4+T cells was decreased in both groups, but no significant difference was seen between the groups. Significant increase of resting energy expenditure and cardiac index was seen until day 3 in the conventional group, whereas those values increased until day 1 in the minilaparotomy group. CONCLUSIONS: Compared with conventional colorectal resection for colon cancer, colorectal resection by minilaparotomy results in a more rapid return of bowel function, less pain and host response. However, the alternations of the host response for surgical stress between the two groups are similar in the early postoperative stage (days 1-2).

Postoperative host responses in elderly patients after gastrointestinal surgery.

BACKGROUND/AIMS: The age-associated dysregulation of hemodynamic, metabolic and immune responses contributes to the high incidence of complications after major abdominal surgery. METHODOLOGY: Ninety-five patients who underwent gastric resection (n=51) and colorectal resection (n=44) were divided according to age into Groups A (n=45, less than 70 years old), B (n=30, 70-79 years) and C (n=20, over 80 years). Flow cytometric analysis of CD4+ lymphocytes for interferon (IFN)-gamma and interleukin (IL)-4 production determined the Th1/2 balance. Energy expenditure was measured by indirect calorimetry, and hemodynamics were studied using pulse dye densitometry. RESULTS: Surgical procedures, operating time, blood loss and morbidity did not significantly differ among the three groups. The cardiac index (CI) in group A and B increased significantly over preoperative levels until POD 3, but there were no significant perioperative changes in the CI levels of group C. Resting energy expenditure levels changed similarly to those of CI. The postoperative Th1/2 ratio decreased from young to elderly to very elderly patients, although no differences were significant before surgery. The postoperative percentage of CD4+IFN-gamma +T cells (Th1) in group C decreased significantly despite of no significant changes in that of group A and B. In contrast, the ratio of CD4+IL-4+T cells (Th2) in the all groups significantly increased after surgery. CONCLUSIONS: Host responses in elderly patients after major abdominal surgery were more hyperdynamic and hypermetabolic than those of young patients. Postoperative dysregulation of the Th1/2 balance was also associated with aging. However, host responses appear to significantly differ between elderly and very elderly patients.

Laparoscopy-assisted right hepatic lobectomy using a wall-lifting procedure.

This article describes a new technique for performing a laparoscopy-assisted right hepatic lobectomy using a hanger wall-lifting procedure. The patient is placed in the left semi-lateral position. A cholecystectomy and hemi-hepatic vascular inflow control are then performed through a midline incision, through which the resected liver can be removed. Next, the right lower chest and right upper abdominal wall are lifted by two wires vertical to the abdominal wall. Two ports, a 5-mm port in right lateral abdomen for forceps and a 12-mm port just right of the umbilicus for the laparoscope, are inserted. The obtained view of the operative field in the right upper abdominal cavity is thus excellent. The laparoscopy-assisted mobilization of the right hepatic lobe is done with the assistance of a hand inserted through the midline incision, including a dissection of the hepato-renal ligament, the right triangular ligament, and the right coronary ligament. A parenchymal dissection is then performed using the Cavitron Ultrasonic Surgical Aspirator (CUSA) and the resected specimen is passed through the midline incision without any morcellation of the liver. This procedure can minimize the length of the wound, while avoiding the lethal complications associated with pneumoperitoneum.

Postoperative metabolic and circulatory responses in patients that express SIRS after major digestive surgery.

BACKGROUND/AIMS: Systemic inflammatory response syndrome (SIRS) includes a number of pathologic states because of its loose definition. This study assessed differences in metabolic and circulatory host responses in various patients with SIRS perioperatively. METHODOLOGY: Fifty-four patients who underwent abdominal surgeries [gastric resection (n=20), colorectal resection (n=24), hepatic resection (n=8)] were divided into two groups: Group A; SIRS (+) on 1 postoperative day (POD), (n=29), B; SIRS (-) on 1 POD, (n=25). The other eight non-operated patients with SIRS caused by infection were enrolled in Group C, as common SIRS. Indirect calorimetry, body impedance measurement to assess water compartments and pulse dye-densitometry for hemodynamic examination were performed in subjects until 14 POD. RESULTS: The ratio of energy expenditure to basal energy expenditure (%REE) was significantly increased postoperatively, and there were significant differences on %REE from 3 POD to 14 POD between groups A and B. However, %REE in group C was 162+/-23%, which was significantly increased compared with that at 1 POD of groups A (130 +/- 17%) and B (125+/-18%). Cardiac output in group A showed a significant increase until 3 POD compared with that in group B but was significantly lower than that in group C. CONCLUSIONS: Subjects with common SIRS caused by infection were significantly more hypermetabolic than subjects with postoperative SIRS. Adequate energy intake and circulatory management should be cautiously determined according to the severity of SIRS.

Hepatic resection leads to predominance of the T helper-2 lymphocyte phenotype.

Recent studies have shown that the type 1/2 T helper (Th1/2) cell balance is shifted toward a Th2-type immune response not only by malignancy but also by surgical stress. This study evaluates in immune responses to surgical stress from liver surgery in comparison with other major abdominal surgeries. PATIENTS AND METHODS:: Eighty-five patients who underwent abdominal surgeries were divided into three groups: hepatic resection (n = 17), gastric resection (n = 38), and colorectal resection (n = 30). Blood sampling was performed before surgery, and on postoperative days (POD) 2 and 14. Cell surface markers were used to characterize Th1/2 balance by flow cytometry and a ratio of the percent IFN-gamma-producing (Th1) cells to IL-4-producing (Th2) cells were expressed as the Th1/2 balance. RESULTS:: The postoperative ratio of Th1 to Th2 was decreased significantly in all subjects to 4.5 +/- 3.0 on POD 2 from 6.7 +/- 4.2. The ratio of Th1 to Th2 in patients who underwent hepatic resection markedly decreased to 2.8 +/- 1.6 on POD 2, significantly different from those in patients undergoing gastric resection or colorectal resection. However, on POD 14 there were no longer any significant differences among the three surgical groups. CONCLUSIONS:: This study shows that hepatic resection induces a more marked shift of the Th1/2 balance toward Th2 than other major abdominal surgeries.

Hepatic resection induces a shift in the Th 1/2 balance toward Th 2 and produces hypermetabolic and hyperhemodynamic states.

BACKGROUND/AIMS: Recent studies have shown that the type 1/2 T-helper (Th 1/2) cell balance is shifted toward a Th 2-type immune response not only by malignancy but also by surgical stress. The present study evaluated surgical stress as a result of liver surgery in comparison with that of other major abdominal surgeries. Immune, metabolic and circulatory responses to surgery were measured for determination of surgical stress. METHODOLOGY: Eighty-five patients who underwent abdominal surgeries were divided into three groups: hepatic resection (n=17), gastric resection (n=38), colorectal resection (n= 30). Blood sampling was performed before surgery, and on postoperative days (POD) 2 and 14. The Th 1/2 helper T cell balance was determined by flow cytometric analysis of interferon-gamma and interleukin-4 expression. Energy expenditure was measured by indirect calorimetry, and hemodynamics was studied using pulse dye densitometry until POD 14. RESULTS: Following surgery Th 1/2 ratios decreased significantly. Additionally, the Th 1/2 balance in patients with hepatic resection on POD 2 was significantly lower than that of patients with other major surgeries. However, on POD 14 there were no significant differences among the three groups. Resting energy expenditure and cardiac index on postoperative days 1 and 3 in patients with hepatic resection increased significantly above levels in the other surgical groups. Conversely, blood volume in the hepatic resection patients was significantly lower than that of other patients until POD 3. Ten patients who developed postoperative complications had significantly lower Th 1/2 ratios and more hypermetabolism. CONCLUSIONS: This study reveals that hepatic resection induces a more marked shift toward a Th 2 helper T cell response and significantly more hypermetabolism than other major surgeries. A distinct pattern of Th 1/2 ratio changes during the early phase of the postoperative course in hepatic resection may be related to changes in metabolism and circulation. Therefore, determination of Th 1/2 balance may be of help in evaluating different surgical procedures, and management of energy intake and circulatory management may be cautiously determined based on the shift in Th 1/2 balance.

Genes encoding pseudo-response regulators: insight into His-to-Asp phosphorelay and circadian rhythm in Arabidopsis thaliana.

In the higher plant, Arabidopsis thaliana, results from recent intensive studies suggested that His-to-Asp phosphorelay mechanisms are involved presumably in propagation of environmental stimuli, such as phytohormones (e.g. ethylene and cytokinin). Here we identified and characterized a set of novel Arabidopsis genes whose products considerably resemble the authentic response regulators (ARR-series) of Arabidopsis in the sense that they have a phospho-accepting receiver-like domain. However, they should be discriminated from the classical ones in the strict sense that they lack the invariant phospho-accepting aspartate site. They were thus named APRRs (Arabidopsis pseudo-response regulators). Two such representatives, APRR1 and APRR2, were characterized extensively through cloning of the corresponding cDNAs, in terms of their structural designs, biochemical properties, subcellular localization in plant cells, and expression profiles at the transcriptional level. The result of in vitro phosphorylation experiment with the Arabidopsis AHP phosphotransmitter suggested that the pseudo-receivers have no ability to undergo phosphorylation. The result of transient expression assay with onion epidermal cells showed that the GFP-APRR1 fusion protein has an ability to enter into the nuclei. The C-terminal domain of APRR1, termed CONSTANS-motif, appears to be responsible for the nuclear-localization. The most intriguing result was that the accumulation of APRR1 transcript is subjected to a circadian rhythm. The APRR1 protein is identical to the one that was recently suggested to interact with the ABI3 (ABISCISIC ACID INSENSITIVE3) protein. These are discussed with special reference to the His-to-Asp phosphorelay signal transduction and circadian rhythm in Arabidopsis thaliana.

Stereoselection in the prins-pinacol synthesis of 2,2-disubstituted 4-acyltetrahydrofurans. Enantioselective synthesis of (-)-citreoviral.

[reaction: see text] The condensation of allylic diols with unsymmetrical ketones proceeds with high stereoselection to form 2,2-disubstituted 4-acyltetrahydrofurans when the alpha-substituents of the ketone differ substantially in size. A Prins-pinacol condensation of this type is the central strategic step in an enantioselective synthesis of (-)-citreoviral.

Can three-dimensional helical CT cholangiography before laparoscopic cholecystectomy be a substitute study for endoscopic retrograde cholangiography?

The study investigated the usefulness of three-dimensional helical computed tomography (3D-CT) before laparoscopic cholecystectomy (LSC) when compared with that of endoscopic retrograde cholangiography (ERC). Forty-five patients referred for LSC, who had undergone 3D-CT cholangiography and ERC simultaneously, participated in the study. Endoscopic retrograde cholangiography and 3D-CT cholangiography were compared in each patient with regard to opacification of the biliary tree, stones, and anatomic variations. Three-dimensional helical CT cholangiography and ERC imaging for predicting operative difficulties in LSC also were compared. The common bile duct and cystic duct were shown in the patients by the images, but the gallbladder was shown in 43 patients (96%) with use of 3D-CT cholangiography and in 36 patients (80%) with use of ERC. A third or more peripheral branches were shown completely with use of 3D-CT cholangiography in 33 patients (73%) and in 32 patients (71%) with use of ERC. Cystic duct stones were found in two of three patients with use of 3D-CT cholangiography and ERC. Common bile duct stones in five of seven patients were detected with use of 3D-CT cholangiography, but all of the common bile duct stones were detected with use of ERC. Anatomic variations of the bile duct were shown in three of four patients by 3D-CT cholangiography and in all patients with use of ERC. No significant differences in findings of the angle of bifurcation and presence of Heister valves between operative easy and complex cases were shown by 3D-CT cholangiography and ERC, despite the more accurate assessment of the cystic duct anatomy with use of 3D-CT cholangiography than with use of ERC. Three-dimensional helical CT cholangiography is useful clinically in preoperative assessment of biliary anatomy, but it is not reliable in the detection of common bile duct stones, and it is not helpful in predicting technical difficulty during LSC.

Compilation and characterization of Arabidopsis thaliana response regulators implicated in His-Asp phosphorelay signal transduction.

His-Asp phosphorelays are evolutionary-conserved powerful biological tactics for intracellular signal transduction. Such a phosphorelay is generally made up of "sensor histidine (His)-kinases", "response regulators", and "histidine-containing (HPt) phosphotransmitters". In the higher plant, Arabidopsis thaliana, results from recent intensive studies suggested that His-Asp phosphorelays may be widely used for propagating environmental stimuli, such as phytohormones (e.g., ethylene and cytokinin). In this study, we first inspected extensively the occurrence of Arabidopsis response regulators in order to compile and characterize them. The results showed that this higher plant has, at least, 14 members of the family of response regulators that can be classified into two distinct subtypes (type-A and type-B), as judged from their structural designs, biochemical properties, and expression profiles. Comparative studies were conducted for each representative (ARR3 and ARR4 for type-A, and ARR10 for type-B). It was suggested that expression of the type-A response regulator is cytokinin-inducible, while that of the type-B response regulator appears to be not. Results from yeast two-hybrid analyses suggested that the type-B response regulator may have an ability to stably interact with a set of HPt phosphotransmitters (AHPs). These and other results will be discussed with special reference to the His-Asp phosphorelay signaling network in Arabidopsis thaliana.

An Arabidopsis protein that interacts with the cytokinin-inducible response regulator, ARR4, implicated in the His-Asp phosphorylay signal transduction.

Previously, Arabidopsis thaliana was shown to possess a set of response regulators (ARR-series), which are implicated in the prokaryotic type of signal transduction mechanism, generally referred to as the His-Asp phosphorylay. Among them, ARR4 is a typical phospho-accepting response regulator, whose expression was recently demonstrated to be rapidly induced by a cytokinin-treatment of the plant. To gain insight into the presumed His-Asp phosphotransfer signaling mechanism as well as the role of ARR4 in this higher plant, in this study we adopt the widely used yeast two-hybrid system, and report the identification of an Arabidopsis protein that has an ability to interact physically with the cytokinin-inducible ARR4 response regulator.

Response regulators implicated in His-to-Asp phosphotransfer signaling in Arabidopsis.

The His to Asp phosphotransfer signal transduction mechanism involves three common signaling domains: the transmitter (or His-kinase), the receiver, and the histidine-containing phototransfer (HPt) domain. Typically, a sensor kinase has a His-kinase domain and a response regulator has a receiver domain containing a phosphoaccepting aspartate, whereas a histidine-containing phototransfer domain serves as a mediator of the histidine-to-aspartate phosphotransfer. This signal transduction mechanism was thought to be restricted to prokaryotes. However, many examples have been discovered in diverse eukaryotic species including higher plants. In Arabidopsis, three sensor kinases have been characterized, namely, ETR1, ERS, and CKI1, which were suggested to be involved in ethylene- and cytokinin-dependent signal transduction pathways, respectively. To date, no response regulator has been discovered in higher plants. We identify five distinct Arabidopsis response regulator genes, each encoding a protein containing a receiver-like domain. In vivo and in vitro evidence that ARRs can function as phosphoaccepting response regulators was obtained by employing the Escherichia coli His-Asp phosphotransfer signaling system.