Treatment of lateral node metastasis from lower rectal cancer

Lateral lymphatics of the rectum originate in the area where branches of the inferior hypogastric plexus and the middle rectal vessels from the internal iliac vessels enter the mesorectum below the level of the peritoneal reflection in the pelvis, then reach the bifurcation of iliac vessels along the internal iliac vessels. Among lateral lymph nodes, the middle rectal, obturator, and internal iliac lymph nodes are important from the viewpoint of both the incidence of metastais and treatment effects. Although total mesorectal excision (TME) had become the standard surgical treatment for rectal cancer by the 1990s, this technique does not treat lateral node metastasis. A randomized clinical trial of TME versus D3 lymphadenectomy (JCOG0212) was started in 2003, and the registration of 701 patients with lower rectal cancer was completed in August 2010. The results of this clinical trial are highly anticipated. In Japan, where the rate of local recurrence after surgery is low, patients at high risk of local recurrence such as those with lateral node metastasis, T4 disease, and multiple lymph node metastases in the mesorectum should be selected to receive preoperative chemoradiation. Japanese surgeons who treat rectal cancers are in an advantageous position because they have the additional measure of lateral node dissection along with TME and chemoradiotherapy.     

Quantitative immunoelectron microscopy of type VI collagen in glomeruli in type I diabetic patients

BACKGROUND: The nature of the extracellular matrix (ECM) accumulating in the glomerular basement membrane (GBM) and mesangium (Mes) in diabetes is unknown. Type IV collagen (Col IV) as estimated by quantitative immunoelectron microscopy was reduced in type I diabetic patients (D) with rapid ("fast-track") compared with slow ("slow-track") development of diabetic nephropathy (DN) lesions and controls (C). Col VI is another ECM component suggested to account for Mes matrix (MM) expansion in DN. METHODS: Col VI ECM density was evaluated in eight "slow-track" {Mes fractional volume [Vv(Mes/glom)] <0.32, duration> 20 years} and seven "fast-track" patients [Vv(Mes/glom)> 0.37, duration <20 years diabetes] and in eight C. Quantitative immunoelectron microscopy was performed using polyclonal antibodies to Col VI. Gold particle density (PDG) in MM and the inner layer (IL) of the GBM was measured using stereologic methods. RESULTS: GBM IL PDG was decreased in both fast-track (1.7 +/- 1.6/microm2, mean +/- SD, P < 0.002) and slow-track (3.9 +/- 2.4, P < 0.02) D versus C (10.8 +/- 7.9). GBM IL PDG was also lower in the fast-track versus slow-track D (P < 0.04). Mes matrix PDG/microm2 was decreased in fast-track D (3.2 +/- 3.6) versus C (14.1 +/- 14.6, P < 0.02); a similar trend was seen in slow-track D (5.7 +/- 5.6, P < 0.1). There was no significant difference in MM PDG between the slow-track and fast-track D. CONCLUSION: Col VI density in MM and GBM is decreased in diabetic patients with slowly and rapidly developing renal lesions. This leaves the nature of ECM accumulation in DN unexplained. At least in part, glomerular ECM compositional change is related to diabetes per se and may be independent of the severity of lesions.     

Safety of laparoscopic intracorporeal rectal transection with double-stapling technique anastomosis

To assess the feasibility and analyze the short-term outcomes of laparoscopic intracorporeal rectal transection with double-stapling technique anastomosis, a review was performed of a prospective registry of 67 patients who underwent laparoscopic sigmoidectomy and anterior resection with intracorporeal rectal transection and double-stapling technique anastomosis between July 2001 and January 2004. Patients were divided into 3 groups: sigmoid colon/rectosigmoid carcinoma, upper rectal carcinoma, and middle/lower rectal carcinoma. A comparison was made of the short-term outcomes among the groups. The number of cartridges required in bowel transection was significantly increased in patients with middle/lower rectal carcinoma, and significant differences were observed in the length of the first stapler cartridge fired for rectal transection. Furthermore, mean operative time and blood loss were also significantly greater in the middle/lower rectum group; however, complication rates and postoperative course were similar among the 3 groups. No anastomotic leakage was observed. Laparoscopic intracorporeal rectal transection with double-stapling technique anastomosis can be performed safely without increased morbidity or mortality.     

Prevalence of Burnout among Internal Medicine and Primary Care Physicians before and during the COVID-19 Pandemic in Japan

Objective To evaluate the change in the prevalence of burnout during the COVID-19 pandemic among internists and primary care physicians in Japan, and to identify factors associated with the exacerbation of burnout among these populations during this period. Methods This was a cross-sectional study based on two web-based surveys conducted in January 2020 (before the declaration of the COVID-19 pandemic) and June 2020 (during the pandemic). The participants were internists and primary care physicians of the Japanese Chapter of the American College of Physicians. The main outcome was the change in the prevalence of burnout between before and during the “first wave” of the pandemic. We also examined factors associated with the exacerbation of burnout during this period. Results Among the 283 respondents in the first survey and 322 in the second survey, 98 (34.6%) and 111 (34.5%) reported symptoms of burnout, respectively. In June 2020, 82 respondents (25.5%) reported that their level of burnout exacerbated compared to January 2020. Only the experience of self-quarantine was associated with the exacerbation of burnout [odds ratio (OR) 3.12; 95% confidence interval (CI) 1.49-6.50; p=0.002], while being a woman, being a resident physician, and an experience of having worked in a prefecture under a state of emergency were not. Conclusions No marked change in the prevalence of burnout among internists and primary care physicians in Japan was observed during the COVID-19 pandemic as a whole. However, self-quarantine was associated with the exacerbation of the burnout level.     

Detailed glomerular ultrastructure in Japanese type 2 diabetic patients by the quick-freezing and deep-etching method

Mesangial expansion and glomerular basement membrane (GBM) thickening did not correlate with urinary albumin excretion (UAE) in type 2 diabetic patients in our previous studies; therefore, it was necessary to elucidate more detailed ultrastructural changes in the early stages of diabetic nephropathy (DN) in type 2 diabetic patients. The quick-freezing and deep-etching (QF–DE) method allows us to examine three-dimensional ultrastructures of human renal glomeruli in vivo at high resolution. The QF–DE method was applied to six type 2 diabetic patients without definable renal diseases other than DN. Four patients were normoalbuminuric (NA) and the other two were microalbuminuria (MA). Three control specimens were the normal parts from nephrectomies due to renal cell carcinomas. Electron microscopic morphometric analyses provided quantitative glomerular structural changes. Replica membranes were prepared by the QF–DE method, and diameters of mesh structures at the GBM and mesangial matrix (MM) were measured on electron micrographs as previously described. By the QF–DE method, both the GBM middle layer and MM were composed of polygonal meshwork structures. The mesh pores of the GBM and MM were more enlarged and irregular in shape in NA diabetic patients than those of the controls, and these ultrastructural changes became more obvious in MA patients. The mesh diameters of the GBM and MM in the diabetic patients were also larger than those of the controls. Such a mesh diameter of the GBM was well correlated with the amount of UAE, while the mesh diameter of MM showed a slight correlation with UAE. Although there were small number of subjects in the present study, the detailed ultrastructural changes in NA and MA type 2 diabetic patients, which had not been disclosed by conventional electron microscopy, were revealed by the QF–DE method. Increased mesh diameters of GBM might be related with the increase of UAE.     

Novel method for the quantitative assessment of cell migration: a study on the motility of rabbit anterior cruciate (ACL) and medial collateral ligament (MCL) cells

A novel method of quantitating cell migration has been proposed for the potential utilization of tissue engineered scaffolds. Applying Alt's conservation law to describe the motion of first passage ACL and MCL cells, we have developed a quantitative method to assess innate differences in the motility of cells from these two ligamentous tissues. In this study, first passage ACL and MCL cells were cultured from four mature New Zealand white rabbits. One side of the cell monolayer was scraped completely away to create a wound model. The cell moved into the cell-free area, and cell density profiles were analyzed at 6 h and 12 h. Values of the random motility coefficient (mu) were then estimated by curve fitting the 6 h and 12 h data to a mathematical model, derived from the conservation law of cell flux. During 6 h of incubation in medium supplemented with 1% FBS, MCL cells (mu(MCL) = 4.63 +/- 0.65 X 10(-6) mm(2)/sec) were significantly (p < 0.05) more mobile than ACL cells (mu(ACL) = 2.51 +/- 0.31 X 10(-6) mm(2)/sec). At 12 h, the MCL cells also appeared to move faster (mu(ACL) = 4.39 +/- 0.63 X 10(-6) mm(2)/sec, mu(MCL) = 6.59 +/- 1.47 X 10(-6) mm(2)/sec), but the difference was not statistically significant (p = 0.18). Exposure of the cells to growth factors PDGF-BB or bFGF for 6 h had no significant effect on the migration of the ACL and MCL cells. However, exposure of the ACL cells (p < 0.05) and the MCL cells (p = 0.19) to 1 ng/mL of PDGFBB for 12 h enhanced their migration. Incubation with a high concentration (100 ng/mL) of PDGF-BB or bFGF at concentrations tested (1 or 100 ng/mL) for 12 h, produced little or no migratory stimulation on these ligament cells. Our findings support the previous qualitative observations made by numerous investigators. The novel methodology developed in this study may provide a basis for tissue engineering, and the results may be applied to tissue reconstruction techniques of the knee ligaments.     

Hematopoietic stem cell and marrow stromal cell for spinal cord injury in mice

We compared the effects of hematopoietic stem cell and marrow stromal cell transplantation for spinal cord injury in mice. From green fluorescent protein transgenic mouse bone marrow, lineage-negative, c-kit- and Sca-1-positive cells were sorted as hematopoietic stem cells and plastic-adherent cells were cultured as marrow stromal cells. One week after injury, hematopoietic stem cells or marrow stromal cells were injected into the lesioned site. Functional recovery was assessed and immunohistochemistry was performed. In the hematopoietic stem cell group, a portion of green fluorescent protein-positive cells expressed glial marker. In the marrow stem cell group, a number of green fluorescent protein and fibronectin-double positive cells were observed. No significant difference was observed in the recovery between both groups. Both hematopoietic stem cells and marrow stromal cells have the potential to restore the injured spinal cord and to promote functional recovery.     

Microinvasive ductal carcinoma (T1mic) of the breast. The clinicopathological profile and immunohistochemical features of 28 cases

Microinvasive ductal carcinoma of the breast, namely ductal carcinoma in situ with microinvasion (T1mic) as defined by the American Joint Committee on Cancer (AJCC) Staging Manual, is a rare disease, although it is increasing because of widespread use of mammography. The aim of the present study was to describe the clinicopathological and immunohistochemical features of this entity. Twenty-eight patients who were diagnosed as T1mic from January 1997 to August 2002 were studied by using 3-5 mm-thick serial sections with hematoxylin-eosin staining. Immunohistochemical staining for the estrogen receptor (ER), progesterone receptor (PR), p53, Ki-67, and HER-2 were performed. All 28 patients were female, with a mean age of 48.8 years. Twenty-six patients (93%) revealed mammographic abnormalities on routine examination. All foci of the invasions were measured using an ocular micrometer. Invasive foci consisted of isolated cells or cell clusters, or appeared as a tongue-like projection of tumor through the basement membrane of the duct of ductal carcinoma in situ (DCIS). The mean number of invasive foci was 3, and the mean size was 0.6 mm. We found that high nuclear grade and predominant comedo subtype of DCIS components were 57.1% and 46.4%, respectively. Twenty-four cases (86%) demonstrated necrosis of DCIS components. Microinvasion was often associated with periductal stromal reaction (71.5%) and/or a lymphocytic infiltration (78.6%). All patients, excluding two, received axillary resection (the mean number of lymph nodes examined per case was 12), and none had lymph node metastasis. The positive expression of ER and PR strongly related to low grade nuclei and non-comedo subtype; however, the positive expression of HER-2 and P53 related to high grade nuclei and comedo subtype (P<0.01). Ki-67 expression was significantly higher in the high grade nuclei group than in the low grade group (P<0.01). Our study suggested that high nuclear grade and comedo DCIS were more aggressive and more common with microinvasion, and that microinvasion is more likely to be multifocal.