Difference in surgical outcomes of rectal cancer by study design: meta-analyses of randomized clinical trials, case-matched studies, and cohort studies.

BACKGROUND: RCTs are considered the standard in surgical research, whereas case-matched studies and propensity score matching studies are conducted as an alternative option. Both study designs have been used to investigate the potential superiority of robotic surgery over laparoscopic surgery for rectal cancer. However, no conclusion has been reached regarding whether there are differences in findings according to study design. This study aimed to examine similarities and differences in findings relating to robotic surgery for rectal cancer by study design. METHODS: A comprehensive literature search was conducted using PubMed, Scopus, and Cochrane CENTRAL to identify RCTs, case-matched studies, and cohort studies that compared robotic versus laparoscopic surgery for rectal cancer. Primary outcomes were incidence of postoperative overall complications, incidence of anastomotic leakage, and postoperative mortality. Meta-analyses were performed for each study design using a random-effects model. RESULTS: Fifty-nine articles were identified and reviewed. No differences were observed in incidence of anastomotic leakage, mortality, rate of positive circumferential resection margins, conversion rate, and duration of operation by study design. With respect to the incidence of postoperative overall complications and duration of hospital stay, the superiority of robotic surgery was most evident in cohort studies (risk ratio (RR) 0.83, 95 per cent c.i. 0.74 to 0.92, P < 0.001; mean difference (MD) -1.11 (95 per cent c.i. -1.86 to -0.36) days, P = 0.004; respectively), and least evident in RCTs (RR 1.12, 0.91 to 1.38, P = 0.27; MD -0.28 (-1.44 to 0.88) days, P = 0.64; respectively). CONCLUSION: Results of case-matched studies were often similar to those of RCTs in terms of outcomes of robotic surgery for rectal cancer. However, case-matched studies occasionally overestimated the effects of interventions compared with RCTs.

Feasibility of thoracoscopic esophagectomy after neoadjuvant chemotherapy.

INTRODUCTION: Minimally invasive esophagectomy has been increasingly accepted to treat esophageal cancer. In Japan, neoadjuvant chemotherapy followed by surgery has become the standard procedure for advanced esophageal cancer. A randomized control study has shown neoadjuvant chemotherapy's survival benefits, but it is unknown whether minimally invasive esophagectomy after chemotherapy is viable. This study investigated the feasibility of thoracoscopic esophagectomy after neoadjuvant chemotherapy. METHODS: From a database of patients with esophageal cancer, 105 patients who had undergone thoracoscopic esophagectomy with radical lymphadenectomy were analyzed retrospectively. Among them, 51 patients had received neoadjuvant chemotherapy with 5-fluorouracil and cisplatin (NAC group). Their operative outcomes, including operative duration, blood loss, the number of dissected lymph nodes, and postoperative morbidity and mortality, were compared with those of 54 patients who underwent surgery without neoadjuvant chemotherapy (control group). The efficacy of neoadjuvant chemotherapy was also assessed. RESULTS: The operating time in the NAC group was significantly longer than in the control group (543 vs 472 min, P < 0.001), but the blood loss was less (323 vs 528 mL, P < 0.001). Recurrent laryngeal nerve palsy was the most frequently observed complication in both groups (27% vs 32%, P = 0.65). No significant differences were observed in the frequency of postoperative complications. There was no mortality in either group. In the NAC group, 43 patients (84.3%) underwent curative resection, and response of more than two-thirds of the pathological tumor was achieved in 11 patients (21.6%), including complete response in one patient (2.0%). CONCLUSION: Thoracoscopic esophagectomy following neoadjuvant chemotherapy could be safely adopted for patients with advanced esophageal cancer.

Reduced-intensity non-T-cell depleted HLA-haploidentical stem cell transplantation for older patients based on the concept of feto-maternal tolerance.

With the recent progress in reduced-intensity conditioning stem cell transplantation (RIST) and taking into consideration the concept of feto-maternal immunological tolerance, we carried out non-T-cell depleted HLA haploidentical RIST from noninherited maternal antigen (NIMA) complementary siblings or offspring donors for four older patients: a patient with myeloplastic syndrome (MDS) and three patients with adult T-cell leukemia (ATL) in partial remission or with progressive disease. All patients showed early, durable engraftment, and no serious toxicities were observed apart from grade III mucositis in one case. Grade II acute GVHD occurred in two cases, which was well-controlled. In one ATL patient whose donor did not have NIMA microchimerism, tacrolimus could not be continued after engraftment due to renal dysfunction, and grade III acute GVHD (gut: stage 4) occurred on day 35. A patient with MDS was free from disease (requiring no transfusions and with a normal bone marrow) for 15 months. Two cases of ATL relapsed. Feto-maternal tolerance may lead to new RIST strategies in the haploidentical reduced-intensity situation, but further evaluation is required.

Cidofovir for treating adenoviral hemorrhagic cystitis in hematopoietic stem cell transplant recipients.

Adenovirus (AdV) infection is an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. We treated 16 patients with AdV hemorrhagic cystitis (HC) following HSCT with cidofovir (CDV; 1 mg/kg/day, three times weekly for 3 weeks). Patients included 10 males and six females with a median age of 50 years (range 10-62). Two of the 16 patients were unevaluable because of early death from nonadenoviral causes. CDV therapy cleared AdV from urine in 12 of 14 patients (86%). Of 14 patients, 10 (71%) showed clinical improvements in HC. Among 14 patients, seven (50%) had avoided renal damage, the most important CDV toxicity. One patient previously treated with foscarnet for cytomegalovirus (CMV) required hemodialysis, and CDV treatment was discontinued. In another patient, CDV treatment was discontinued because of grade 2 nephrotoxicity. Four patients became positive for CMV antigenemia while being treated with CDV, and two developed herpes simplex virus (HSV) stomatitis while being treated with CDV. CDV proved effective in treating AdV HC in transplant patients. However, CDV at 1 mg/kg/day given three times weekly failed to prevent breakthrough infection with CMV and HSV in some patients.

Nitric oxide induces a decrease in the mitochondrial membrane potential of peripheral blood lymphocytes, especially in natural killer cells.

Increased levels of nitric oxide (NO) at an inflammatory site may affect the biological activity of lymphoid cells. To investigate the effects of NO on the immune system, we measured the mitochondrial membrane potential (delta psi m) of the peripheral blood lymphocytes (PBL) cultured with a chemical NO donor. PBL from healthy volunteers were cultured with NOC18, a NO-generating compound, at various concentrations. The delta psi m of the PBL was measured by flow-cytometry using 3,3-dihexyloxacarbocyanine iodide (DiOC6(3)). NOC18 induced a decrease in the delta psi m of the PBL in a dose-dependent fashion, induced an increase in the levels of reactive oxygen species (ROS), and caused these cells to undergo apoptosis. Dual-color staining of the delta psi m and lymphocyte surface markers demonstrated that CD3-CD56+ natural killer (NK) cells were responsive to NO. Trolox, a vitamin E analog, partially reversed the NO-induced decrease in the delta psi m of the PBL. We showed that the delta psi m of peripheral NK cells were decreased by NO, which suggests that abundant NO at an inflammatory site may impair NK cell function.

L-asparaginase induced complete remission in Epstein-Barr virus positive, multidrug resistant, cutaneous T-cell lymphoma.

A 30-year-old man was admitted to our hospital with subcutaneous tumors and a high fever. Based on biomicroscopic findings of the tumor, the patient was diagnosed as having diffuse, medium, well-differentiated malignant lymphoma. Immunochemical analysis showed that CD3, CD4, CD25, and TCR beta were positive, and in situ hybridization revealed Epstein-Barr virus-encoded small RNAs in the nuclei of the lymphoma cells. Despite the patient's resistance to multidrug therapy, complete remission was achieved using L-asparaginase. This case is unique because of its peculiar clinical course and a possible association with the Epstein-Barr virus. L-asparaginase may be an important treatment in other patients who exhibit some of these characteristics.

Expression of Thrombomodulin in the epithelium of the urinary bladder: a possible source of urinary thrombomodulin.

Thrombomodulin (TM) is an endothelial thrombin receptor which acts as a natural anticoagulant through inactivation of the procoagulant activity of thromin. In the present study, we demonstrated that TM is expressed on the urinary bladder epithelium. The cell line BOY established from human transitional cell carcinoma of the urinary bladder also expressed the TM message (3.7kb). These cells express an 85 kDa TM protein which is identical in size to that of MEG-01, a human megakaryoblastic cell line, reported previously. We also ascertained the expression and localization of TM in the human urinary bladder by immunohistochemical staining. TM was localized in the membranes of the transitional epithelium and the cytoplasmic region of umbrella cells. The expression of TM in the transitional epithelium increased with worsening pathological status of cystitis. Based on these results, we concluded that TM is expressed in the urinary bladder. Further, soluble TM in urine may be partially derived from the urinary bladder. At present, the physiological significance of TM expression in the urinary bladder remains to be elucidated.

Allogenic bone marrow transplantation as a treatment for adult T-cell leukemia.

We performed allogenic bone marrow transplantation (BMT) in two adult T-cell leukemia (ATL) patients with HLA-identical siblings as donors. One patient, with acute ATL, relapsed 3 months after BMT. The other, with chronic ATL, has become free of disease over 18 months after the BMT from his human T-cell lymphotropic virus type 1 (HTLV-1)-negative sibling, and we were unable to detect HTLV-1 in the patient's peripheral blood. Based on our results and those of others, although there have been limited numbers of patients, BMT may represent the only potentially curative treatment for ATL, and the presence of graft-vs.-host disease tends to be related to good results, which suggests the possibility that graft-vs.-leukemia effects may play an important role in allogenic BMT for ATL.

The correlation between erythropoiesis and thrombopoiesis as an index for pre-operative autologous blood donation.

We have previously reported that the platelet count and an increase in platelet number reflect individual erythropoietic capacity in pre-operative autologous blood donation (PABD). We have examined the correlation between erythropoiesis and thrombopoiesis by quantitative in vitro determination of thrombopoietin (TPO), erythropoietin (EPO), and interleukin-6 (IL-6) in patients with PABD. A sequential increase in platelet count with donation could not be explained by an increase in TPO. TPO showed a tendency to be inversely related to the pre-donation platelet count, and to be related to the pre-donation hemoglobin level. There was an inverse relationship between the TPO and EPO levels. As seen with these results, a high erythropoietic state induces restraint of thrombopoiesis, and a low erythropoietic state induces an increase in thrombopoiesis. These effects modulate EPO and TPO via negative feedback. These results provide some practical important information for performing autologous blood donation. Further studies are needed to elucidate the details of these correlations.

The platelet level indicates the erythropoietic capacity for preoperative autologous blood donation.

UNLABELLED: The erythropoietic capacity for preoperative autologous blood donation (ECPABD) shows marked inter individual variability. This study was performed to evaluate factors useful to predict individual ECPABD from data available before the first donation. The subjects consisted of 74 adult patients who received autologous blood donation, with a mean of 61 +/- 12.8 yr (SD). We classified the patients into four groups using our criteria for evaluating the ECPABD and investigated the relationships among age, disease, pre-platelet count, and the rate of platelet increase. RESULTS: (1) Advanced age and the status of disease were not distinctly correlated with low ECPABD. (2) Patients with a high pre-platelet levels had a low ECPABD regardless of the haemoglobin. (3) Patients in which the platelet count increased in accordance with the level of collection exhibited low pre-platelet counts and high ECPABD. CONCLUSION: In patients with high pre-platelet levels, we reduced the amount collected, considered early use of recombinant human erythropoietin and reevaluated the application of autologous blood donation.

Secondary monocytic leukemia with rearrangement of the MLL gene occurring during the course of adult T-cell leukemia.

In June 1994, a 39 year-old male with adult T-cell leukemia was admitted to our hospital and received combination chemotherapy including epipodophyllotoxin for approximately 1 year. The monocyte count increased gradually beginning in April 1995, accelerating to 100 x 10(9)/l in January 1996, when he was diagnosed with acute monocytic leukemia. Inv(11)(q21;q23) x 2 was recognized at that time by chromosome analysis, and rearrangement of the MLL gene was shown by Southern blot analysis. From the clinical course and subsequent examinations, the case was regarded as epipodophyllotoxin-related secondary leukemia. Recently, epipodophyllotoxin has frequently been used as a treatment agent for adult T-cell leukemia. It is valuable to note that secondary leukemia may follow even such an aggressive leukemia as adult T-cell leukemia.

Establishment of a human myeloma cell line with growth-promoting activity for bone marrow-derived fibroblastoid colony-forming cells.

A human myeloma cell line, PCM6, was newly established from peripheral blood of a patient with advanced IgG myeloma by addition of recombinant interleukin-6 (IL-6) in culture. PCM6 cells had a morphology typical of mature plasma cells. Cytogenetic and surface marker studies confirmed that PCM6 cells were identical to fresh myeloma cells. Coculture of PCM6 cells with normal bone marrow mononuclear cells resulted in increased colony size of bone marrow-derived fibroblastoid colony-forming cells (CFU-F). Conditioned medium of PCM6 (PCM6-CM) cells increased the CFU-F colony size in a dose-dependent manner. The activity was labile to trypsin treatment but was heat stable (60 degrees C, 30 minutes). Molecular weight of the activity was approximately 165 kd by Sephacryl S-300 gel filtration. Platelet-derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), and IL-1 beta were not detectable in the conditioned medium. These findings suggest that in some myeloma cases, bone marrow stroma may be affected by CFU-F growth-promoting activity.

Immediate-type allergy related to okra (Hibiscus esculentus Linn) picking and packing.

Two workers (cases A and B) engaged in picking and packing okra who had complaints of work-related allergic symptoms showed distinct positive intradermal reactions to two brands of okra extracts only with thresholds of 1 x 10(-8) w/v for Case A and 1 x 10(-6) w/v for Case B. Both also showed positive reactions to okra extracts in the Prausnitz-Küstner test and in the provocative nasal test. The radioallergosorbent test scores to the okra extract were determined to be 2 (defined as clear positive) for Case A and 1 (border line) for Case B. These findings indicated that the allergic conditions of these cases were from an IgE-mediated immediate-type allergy induced by handling okra. To confirm the etiology of the two cases 14 farmers engaged in picking and packing okra were examined. Among them, 8 subjects (57%) showed positive intradermal reactions to okra extracts. A close association between intradermal reactions to okra extracts and complaints of work-related allergic symptoms was seen in these subjects. These results confirm that the okra may be capable of inducing IgE-mediated immediate-type allergy to workers handling okra.

Parvovirus B19-associated haemophagocytosis in Evans syndrome: aplastic crisis accompanied by severe thrombocytopenia.

A 36-year-old man who had been treated for Evans syndrome (ES) developed an aplastic crisis caused by acute human parvovirus B19 (HPV) infection. Profound thrombocytopenia (8.0 x 10(9)/l) followed with a sudden increase in platelet-associated IgG (PAIgG) (1376.9 ng/10(7) plts). Bone marrow examination revealed a considerable number of haemophagocytic histiocytes without any disturbance of megakaryopoiesis. To our knowledge this is the first case of aplastic crisis with virus-associated haemophagocytosis in a patient with ES, which provides an interesting insight into the mechanisms for thrombocytopenia in HPV infection.

[A case of primary non-Hodgkin lymphoma of the adrenal gland presenting with Addison's disease].

A 69-year-old male was admitted to our hospital complaining of skin pigmentation. Masses in bilateral adrenal glands were noted on computed tomography. An exploratory laparotomy revealed malignant lymphoma confined to the bilateral adrenal glands. Histological diagnosis was diffuse mixed-cell type, B-cell lymphoma. Laboratory tests disclosed an elevated ACTH level and decreased urinary 17KS and 170HCS secretion. Based on hypofunction of adrenal glands and skin pigmentation, the patient was diagnosed as having Addison's disease. After complete remission with combination chemotherapy, adrenal function recovered normal and pigmentation disappeared, Addison's disease is an extremely rare complication of primary malignant lymphoma of the adrenal gland.

Recent trends in bagassosis in Japan.

The only workers presently exposed to bagasse dust in Japan are the employees of sugar refineries and lacquerware factories. A follow up study of six former cases of bagassosis from among the retired employees of a paper board factory, closed since 1973, showed that none of the subjects still had bagassosis. Examinations of 70 employees of a sugar refinery for allergic reactions also showed no case of bagassosis. Seven cases with suspicious shadows of bagassosis on chest radiographs and four cases with positive serum precipitin to stored bagasse were, however, found among those 70 subjects. The results show the disappearance of a past episode of bagassosis and the possibility of a new occurrence of bagassosis among the employees of sugar refineries and lacquerware factories in the near future in Japan.

[i(17q) appearing in acute phase in Ph1-negative, BCR-negative CML].

A 36-year-old woman was referred to our hospital because of splenomegaly in February 1989. The leukocyte count was 55,500/microliter without hiatus leukemicus. The leukocyte alkaline phosphatase score was low (29). The bone marrow showed myeloid hyperplasia (24.8% myeloblasts) but no dysplastic change. The karyotype of the bone marrow cells was 46, XX and a diagnosis of Ph1 (-) CML was made. Treatment with VCR, 6MP and prednisolone made 7-month duration chronic phase, but the abnormal karyotype.[46, XX, i(17q)] gradually increased to 100% of bone marrow cells. The patient died in June 1990. The evidence that not only a BCR rearrangement but also messages of BCR/ABL fusion gene were negative made us able to differentiate this case from Ph1(-), BCR(+) CML. The addition of an i(17q) results in partial monosomy of 17q (17q13;p53 gene) and partial trisomy of 17q (17q11.2-12;G-CSF gene). We examined the rearrangement of p53 gene and G-CSF-dependent tumor cell growth in vitro, demonstrating one allelic loss of p53 gene and independent cell growth on G-CSF respectively. It is thought that in Ph1 (-), BCR (-) CML as well as in Ph1 (+) CML, an i(17q) is related to the progression but not to the initiation of these leukemias. However the precise mechanism, including p53 gene inactivation by point mutation, is still to be elucidated.

Allergic contact dermatitis in shiitake (Lentinus edodes (Berk) Sing) growers.

A 42-year-old female shiitake grower was investigated to clarify the etiology of skin lesions which developed during the planting of shiitake hyphae into bed logs. She complained of repeated eczematous skin lesions during the planting season, from March to July, for 10 years. She handled 7,000 pieces of small conic blocks made of beech, with shiitake hyphae attached to their surface, per day, and 300,000 pieces altogether per season. She was positive on patch testing with extracts of shiitake hyphae. In contrast, female shiitake growers with skin lesions associated with work other than planting, and without skin lesions, were negative on patch testing to the hyphae. Moderate allergenicity was observed to extracts of shiitake hyphae in a guinea pig maximization test. These findings indicated the etiology of skin lesions in shiitake growers to be allergic contact dermatitis induced by shiitake hyphae.