Usefulness of the one-step technique in functional end-to-end anastomosis for colonic surgery: results of a prospective multicentre cohort study from the Japanese KYCC group.

BACKGROUND: Although functional end-to-end anastomosis (FEEA) using a stapler in the colorectal field has been recognised worldwide, the technique varies by surgeon, and the safety of anastomosis using different techniques is unknown. METHODS: This multicentre prospective observational cohort study was conducted by the KYCC Study Group in Yokohama, Japan, and included patients who underwent colonic resection at seven centres between April 2020 and March 2022. This study compared the incidence of surgery-related abdominal complications (SAC: anastomotic leakage [AL], anastomotic bleeding, intra-abdominal abscess, enteritis, ileus, surgical site infection, and other abdominal complications) between two different methods of FEEA (one-step [OS] method: simultaneous anastomosis and bowel resection; two-step [TS] method: anastomosis after bowel resection). Complications of Clavien-Dindo classification grade 2 or higher were assessed. RESULTS: Among 293 eligible cases, the OS and TS methods were used in 194 (66.2%) and 99 (33.8%) patients, respectively. The baseline characteristics were similar between the groups. The OS method used fewer staplers (three vs. four staplers, p < 0.00001). There were no significant differences in SAC rate between the OS (19.1%) and the TS (16.2%) groups (p = 0.44). The OS group had four cases (2.1%) of AL (two patients; grade 3, two patients; grade 2) while the TS group had one case (1.0%) of grade 2 AL (p = 0.67). Multivariate logistic regression analysis showed that male sex (odds ratio [OR] 3.95; p < 0.00001), an open surgical approach (OR 2.36; p = 0.03), and longer operative duration (OR,2.79; p = 0.002) were independent predictors of complications, whereas the OS method was not an independent predictor (OR 1.17; p = 0.66). CONCLUSIONS: The OS and the TS technique for stapled colonic anastomosis in a FEEA had a similar postoperative complication rate. TRIAL REGISTRATION NUMBER: UMIN000039902 (registration date 23 March 2020).

Application and outcomes of a standardized lymphadenectomy in laparoscopic right hemicolectomy requiring ligation of the middle colic artery.

BACKGROUND: Complete mesocolic excision with central vessel ligation may be important for accurate staging and improving the prognosis of right-sided colon cancer. Although the procedure is often performed laparoscopically, approaching the middle colic artery (MCA) is technically demanding, especially when complete ligation of arteries at their roots is desired. We standardized our laparoscopic approach by establishing the dissection boundary along the superior mesenteric artery to achieve D3 lymphadenectomy in the region of the MCA. The aim of the present study was to evaluate, on the basis of perioperative and short-term oncologic outcomes, the feasibility and safety of our technique METHODS: We conducted a retrospective study on consecutive patients with cancer located at the ascending colon and transverse colon who had laparoscopic right hemicolectomy requiring ligation of the MCA. RESULTS: There were 41 patients (22 males, median age 71 years [range 49-86] years). The median operation time was 285 min, and blood loss volume was 40 mL. Conversion to open surgery was required in 1 case. Complications that were Clavien-Dindo grade III or above occurred in 3 patients (7.3%). There was no anastomotic leakage. The median number of lymph nodes harvested was 46. CONCLUSIONS: Our technique was shown to be a safe, feasible, and useful strategy for performance of right hemicolectomy requiring ligation of the MCA in cases of colon cancer. The technique facilitates maximal lymph node dissection. Having obtained favorable outcomes, we look forward to investigation into long-term outcomes.

Adipocytokine, progranulin, augments acetylcholine-induced nitric oxide-mediated relaxation through the increases of cGMP production in rat isolated mesenteric artery.

AIM: Progranulin (PGRN) is a novel adipocytokine with anti-inflammatory effects in vascular cells. The aim of this study was to clarify the effects of PGRN on reactivity of isolated blood vessel. METHODS: Isometric contraction of rat isolated superior mesenteric artery was measured. RESULTS: Pre-treatment with PGRN (10-100 ng mL-1 , 30 min) had no effect on noradrenaline- or 5-hydroxytriptamine-induced contraction. On the other hand, pre-treatment with PGRN (100 ng mL-1 ) augmented acetylcholine (ACh; 30 nm)-induced endothelium-dependent relaxation. Pre-treatment with PGRN (100 ng mL-1 ) augmented ACh (10 µm)-induced nitric oxide (NO)-mediated relaxation in the presence of indomethacin (10 µm), a cyclooxygenase inhibitor, and tetraethyl ammonium (10 mm), a non-selective potassium channel blocker. In contrast, pre-treatment with PGRN (100 ng mL-1 ) had no effect on ACh-induced endothelium-derived hyperpolarizing factor-mediated relaxation. Pre-treatment with PGRN (100 ng mL-1 ) had no effect on ACh (10 µm, 1 min)-induced endothelial NO synthase phosphorylation (at Ser1177) as determined by Western blotting. Pre-treatment with PGRN (100 ng mL-1 ) augmented an NO donor, sodium nitroprusside (SNP; 30 nm-1 µm)- but not a membrane-permeable cGMP analogue, 8-bromo-cGMP-induced relaxation. In the presence of 3-isobutyl-1-methylxanthine (100 µm), a phosphodiesterase inhibitor, pre-treatment with PGRN (100 ng mL-1 ) increased SNP (30 nm, 5 min)-induced cGMP production as determined by enzyme immunoassay. CONCLUSION: We for the first time demonstrate that PGRN augments ACh-induced NO-mediated relaxation through the increases of cGMP production in smooth muscle. These results indicate PGRN as a possible pharmacotherapeutic target against cardiovascular diseases including obesity-related hypertension.

Increased susceptibility to ischemic brain injury in cyclooxygenase-1-deficient mice.

Cyclooxygenase-1 (COX-1), a rate-limiting enzyme in the synthesis of prostanoids, is involved in selected vasodilatatory responses of the cerebral circulation. Cyclooxygenase-1-null mice were used to determine whether COX-1 influences cerebral ischemic damage. The middle cerebral artery was occluded in COX-1 -/- and +/+ mice (n = 9/group), and lesion volume was determined in thionin-stained sections 24 or 96 hours later. Middle cerebral artery occlusion produced larger infarcts in COX-1 -/- mice, both at 24 (35 +/- 17%; P < 0.05) and 96 hours (41 +/- 16%; P < 0.05) after ischemia. The enlargement was not due to increased susceptibility to glutamate excitotoxicity, because microinjection of N-methyl-D-aspartate or kainate in the parietal cortex produced comparable lesions in COX-1 +/+ and -/- mice ( P > 0.05; n = 8/group). To examine the contribution of hemodynamic factors to the enlargement of the infarct, cerebral blood flow was monitored by laser-Doppler flowmetry in the ischemic territory (n = 6/group). Although the reduction in cerebral blood flow was comparable in the ischemic core ( P > 0.05), at the periphery of the ischemic territory the reduction was greater in COX-1 -/- mice (-58 +/- 4%) than in COX-1 +/+ mice (-34 +/- 5%; P < 0.05). It is concluded that mice lacking COX-1 are more susceptible to focal cerebral ischemia, an effect that can be attributed to a more severe cerebral blood flow reduction in vulnerable regions at the periphery of the ischemic territory. Thus, the vascular effects of COX-1 may contribute to maintain cerebral blood flow in the postischemic brain and, as such, play a protective role in ischemic brain injury.

Technetium-99m(V)-DMSA and thallium-201 in brain tumor imaging: correlation with histology and malignant grade.

UNLABELLED: This study was performed to compare imaging ability between pentavalent 99mTc-DMSA and 201TlCl in primary and metastatic brain tumors and to evaluate the relationship between retention and histologic malignancy. METHODS: Patients with a brain tumor were selected by MRI and/or CT. Dynamic, early and delayed static SPECT images of the brain were obtained immediately, 30 min and 3 hr after intravenous administration of approximately 555 MBq 99mTc(V)-DMSA and 111 MBq 201Tl-Cl, respectively. Both studies were performed on separate days within a week. Uptake ratios, retention ratio and retention index were calculated and compared with tumor histology and malignancy grade. RESULTS: One-hundred six studies were performed on 100 patients and 118 lesions were demonstrated: 16 glioblastomas, 13 anaplastic astrocytomas (Grade III), 19 astrocytomas (Grade II), 29 meningiomas, 11 schwannomas and 14 metastases. Approximately 93% and 88%, respectively, of primary and metastatic brain tumors were demonstrated by 99mTc(V)-DMSA and 201TlCl. The early uptake ratios were closely related to the tumor vascularity, but had no statistically significant difference in the tumor histology or histologic malignancy on either radiopharmaceuticals. The delayed uptake ratio, retention ratio and retention index were higher in malignant tumors than benign ones on 99mTc(V)-DMSA, however, there was no statistically significant difference between benign and malignant tumors on 201TlCl. CONCLUSION: Technetium-99m(V)-DMSA washout from the tumor was highly dependent upon its histology and histologic malignancy. The delayed uptake ratio, retention ratio and retention index significantly reflected tumor histology and clearly distinguished between benign and malignant tumors with a statistically significant difference. There was no statistically significant difference in 201TlCl uptake or washout among the brain tumors. Technetium-99m-DMSA is superior to 201TlCl in imaging quality, sensitivity to brain tumors and specificity for differentiating benign tumors from malignant ones. These results could suggest the clinical utility of 99mTc(V)-DMSA in imaging primary and metastatic brain tumors and differentiating their histological malignancy grade noninvasively.

Induction of tumor degeneration by sodium benzylideneascorbate.

Intravenous administration of sodium benzylideneascorbate (SBA) rapidly necrotized inoperable human lung cancer, and induced degeneration of 3'-methyl-4-dimethylaminoazobenzene-induced rat hepatocellular carcinoma (vacuolar, eosinophilic degeneration, nuclear debris) without affecting the serum glutamic oxaloacetic transaminase, gamma-glutamyl transpeptidase and total protein levels. Cultured normal human lung and skin fibroblasts, and human glioma and glioblastoma cell lines were relatively resistant to SBA, when compared to human myelogenous leukemic cell lines. SBA had no apparent host immunopotentiation activity such as stimulation of cytokine action or production; activation of monocyte or polymorphonuclear cells; or modulation of poly (ADP-ribose) glycohydrolase activity. The data suggest that the antitumor activity of SBA might be produced by direct action of authentic SBA or its metabolized form(s), rather than by immunopotentiation of the hosts.

Effect of sodium benzylideneascorbate on chemically-induced tumors in rats.

Intravenous administration of sodium benzylideneascorbate (SBA) dose-dependently induced degeneration (vacuolar and eosinophilic degeneration and cell shrinkage and nuclear condensation, which are characteristic of apoptotic cell death) of 3'-methyl-4-dimethylaminoazobenzene-induced rat hepatocellular carcinoma. SBA did not significantly induce lymphocyte infiltration and fibrosis in the liver, nor damage the gross morphology of kidney and spleen cells. SBA failed to stimulate the production of tumor necrosis factor and interleukin-1 beta in both in vitro and in vivo systems. These results may suggest a direct antitumor action of SBA via induction of apoptosis in the tumor. However, SBA did not significantly affect the doubling time, or the extent of invasion and differentiation of dimethylhydrazine-induced colon carcinoma in rats. These data suggest that the conditions of SBA administration should be re-established for each tumor sample to produce maximum antitumor activity.

Rat hepatocellular carcinogenesis and proliferating cell nuclear antigen expression induced by 3'-methyl-4-dimethylaminoazobenzene.

The experimental conditions for the induction of rat hepatocellular carcinoma by oral administration of 3'-methyl-4-dimethylaminoazobenzene (DAB) were established. Hematoxylin-eosin (HE) staining of the liver sections revealed that precancerous lesions, characterized by small proliferation nest, hyperplastic nodule, oval cell and adenofibrosis, were observed 2 months after DAB administration. The highest incidence of hepatocellular carcinoma, trabecular carcinoma and mixed form of hepatocellular and cholangiocarcinoma was observed after 3-5 months and remained for an additional 2 months, even if the rats were continuously fed with DAB-free fodder. Immunohistochemical study with monoclonal antibody against proliferation cell nuclear antigen (PCNA) revealed that the relative number of PCNA-positive cells increased with the progress of the carcinoma. The present study confirms the previously reported usefulness of the PCNA immunostaining method for prognosis and assessment of the malignancy of carcinoma.

Distribution of TNF endogenously induced by various immunopotentiators and Lactobacillus casei in mice.

Intravenous administration of heat-killed Lactobacillus casei YIT 9018 (LC) elicited endogenous cytotoxic factor (CF) production in ICR mice, peaking in serum after 2 h and declining gradually to basal level at 23 h. The endogenous CF production was significantly enhanced by priming with high molecular-weight lignins and glucans, but not by phenylpropenoid precursors or partially hydrolyzed products of glucans. The extent of stimulation of CF production by these priming agents was positively related to that of tumor necrosis factor (TNF) production, as judged by enzyme-linked immunosorbent assay. Endogenously produced TNF was concentrated more in liver, lung and intestine, as well as in serum, than in other organs. Histochemical examination revealed a significant increase in the number and swelling of Kupffer cells and sinusoidal endothelium in the liver of the treated mice.

[Preliminary screening for antiviral AIDS drugs. VIII. Report for fiscal year 1995].

Preliminary screening of antiviral AIDS drugs has been carried out using three different in vitro assay systems. Among 96 samples of different origin tested, two were shown to inhibit the growth of HIV in vitro. One of the positive samples (plant origin) has hopeful signs, as the ranges of effective doses are wider than those of most of positive samples which had been found by us.

[Pure red cell aplasia with thymoma, myasthenia gravis and normal pressure hydrocephalus].

Cases of pure red cell aplasia with thymoma and myasthenia gravis are rare. We described a patient who had concomitant pure red cell aplasia, thymoma, myasthenia gravis and a normal pressure hydrocephalus. A 63-year-old man with disturbances of gait, left blepharoptosis and anemia was presented to our hospital. Laboratory examination on admission revealed severe anemia. Bone marrow aspirates showed erythroid hypoplasia of marked degree. Chest x-ray and chest CT revealed a tumor to the right of cardiac wall. The tensilon chloride test and antiacetylcholine receptor antibody were positive. A hydrocephalus was demonstrated with brain CT. Cerebrospinal fluid pressure was in the normal range. He was diagnosed as having pure red cell aplasia with thymoma, myasthenia gravis and a normal pressure hydrocephalus. This appears to be a fairly rare case. It seems important to consider that a normal pressure hydrocephalus may have immunological disorders.

[Multicentric Castleman's disease with lymphoid interstitial pneumonia died of aggressive course with adult respiratory distress syndrome].

A 49-year-old man was admitted to our hospital with anemia and hypergammaglobulinemia. Physical examination revealed superficial lymph node swelling and no hepatosplenomegaly. Laboratory findings showed WBC 5,300/microliters with normal hemogram, microcytic and hypochromic anemia. Total protein was 11.5 g/dl and immunoglobulinemia (IgG 10,100 mg/dl, IgA 295 mg/dl, IgM 160 mg/dl) was observed without M-component in serum and urine. The CD4/CD8 ratio of lymphocyte subsets was 0.58 and the tuberuculin skin test was negative. Urinary protein was positive and renal biopsy disclosed plasma cell infiltration. Lymph node biopsy revealed multiple lymphoid follicles and infiltration of plasma cells in the interfollicular areas. A diagnosis of multicentric Castleman's disease (MCD) was made baredon clinical findings and lymph node biopsy. After therapy with plasmapheresis and the CHOP regimen, he was given etoposide. Although discharged with clinical improvement and a decrease of serum IgG, he was readmitted because of pyrexia after 4 days and died of pneumonia with adult respiratory distress syndrome. The autopsy revealed lymphoid interstitial pneumonia. It seems important to notice that some of MCD have poor prognoses because of accompanying immunodeficiency.

[Autoimmune hemolytic anemia associated with multicentric Castleman's disease with a 28-year history].

A 49-year-old female admitted because of anemia. had skin rashes since age 20. Generalized lymphadenopathy and fever appeared and the patient was diagnosed as multicentric Castleman's disease (MCD) at 40 years of age. Lymphadenopathy and fever improved with combined chemotherapy. In November, 1992, anemia increased with reticulocytosis (11.8%) and laboratory examination revealed a positive result for Coombs test and increased indirect bilirubin. A diagnosis of autoimmune hemolytic anemia (AIHA) was made. Steroid and plasmapheresis showed temporary effects, but anemia relapsed when steroids were decreased. Immunosuppressive drugs, vincristine and danazole were ineffective. Anemia improved on the second attempt at steroid therapy. The level of Hb rose to 11.2 g/dl after 3 months. The relationship between MCD and AIHA was discussed.

[Perioperative management of life-threatening intra-abdominal bleeding with intra-aortic balloon occlusion catheter].

Intra-thoracic aortic clamping using an intra-aortic balloon occlusion catheter (IABOC) is employed for patients with life-threatening intra-abdominal and/or extra-abdominal bleeding in spite of massive transfusion. For perioperative management, we inserted an IABOC preoperatively into a 59-year-old man with life-threatening intra-abdominal bleeding from an abscess formed around his traumatically injured pancreas. We could perform a safe operation in which bleeding was controlled by intermittently occluding the IABOC and the patient was thus prevented from developing into severe hemorrhagic shock. We experienced a usefulness of IABOC for a patient with life-threatening intra-abdominal bleeding uncontrolled due to intra-abdominal adhesion during the perioperative period. However, organ dysfunctions caused by ischemia and reperfusion following intra-aortic balloon occlusion must be prevented by shortening the occlusion time through use of an intermittent method such as described above.

[Treatment of adult acute lymphoblastic leukemia by KHALL-93--long-term outcome].

Twelve previously untreated adult patients with acute lymphoblastic leukemia were treated with a KHALL-93 regimen. The mean age was 46.9 years. Four patients (1/3) were over 60 years old, and 5 were Ph1 positive (42%). The complete remission rate was 100%. The 5-year survival was 50% (6/12). The 5-year event-free survival was 50% (6/12) in total, 71% (5/7) in Ph1 negative patients, and 63% (5/8) in patients younger than 60 years old. These results indicate that a KHALL-93 regimen is an effective therapy for adult acute lymphoblastic leukemia.