Early stoma closure after low anterior resection is not recommended due to postoperative complications and asymptomatic anastomotic leakage.

The safety of early stoma closure after lower anterior resection (LAR) for rectal cancer remains controversial. In this study, patients scheduled to undergo LAR and stoma creation for rectal cancer were recruited. In absence of anastomotic leakage on radiological examination, closure of the diverting ileostomy was performed within 2 weeks. The primary endpoint was incidence of the colorectal anastomosis leakage after early stoma closure. Because of the slow accrual rate, the study was closed before recruitment reached the planned number of patients (n = 20). Among the 13 patients enrolled between April 2019 and March 2021, early stoma closure was performed in seven patients (53.8%). Non-clinical anastomotic leakage, leakage identified only on radiological examination, occurred in five cases, resulting in rescheduling of stoma closure. One patient did not undergo early stoma closure due to ileus. After stoma closure, colorectal anastomotic leakage manifested in one case; its incidence rate was 14.2%. Surgical site infection occurred in 42.8% of patients. This study revealed that asymptomatic anastomotic leakage occurred frequently. Considering the low rate of successful cases and the high rate of complications, early stoma closure within 2 weeks after LAR should not be performed routinely. Trial registration: (UMIN000036382 registered on 03/04/2019).

The safety of early versus late ileostomy reversal after low anterior rectal resection: a retrospective study in 47 patients.

BACKGROUND: This study aimed to clarify the safety of early closure in diverting ileostomy with lower anterior rectal-cancer resection. METHODS: We retrospectively reviewed consecutive 47 patients who underwent diverting ileostomy with lower rectal-cancer resection between May 2009 and October 2017. The results of the stoma closure were compared between patients who underwent stoma closure within 90 days (early closure [EC] group) and those who underwent late closure (LC group; closure after 90 days). Because of the small sample size, the frequency of severe complications post closure was analyzed. RESULTS: Among 47 patients, 29 were in the EC group. Postoperative complications occurred in 48.3% (14/29) and 27.8% (5/18) of patients in the EC and LC groups, respectively. This difference was due to minor complications (Clavien-Dindo Classification I/II), such as superficial incisional surgical site infections (n=5) in the EC group. The rate of severe complications (Clavien-Dindo Classification ≥ III) was similar between the groups (20.7% vs. 16.7%, p=1, Fisher's exact test). CONCLUSIONS: No association was observed between the time of closure and development of major complications; however, there was an increased likelihood of minor complications after EC. This study provides a basis on which future treatment guidelines for early stoma closure may be developed without affecting patient quality of life.

Lymph node retrieval after colorectal cancer surgery: a comparative study of the efficacy between the conventional manual method and a new fat dissolution method.

PURPOSE: This study compared the efficacy of two different methods for lymph node (LN) searching after colorectal cancer surgery: the fat dissolution and the conventional manual method. METHODS: For the fat dissolution method, we used a commercially available solution of collagenase and lipase (FD group). The primary endpoint was the number of identified LNs in the FD group compared to an historical control (control group) after adjusting by propensity score matching. RESULTS: Using 37 matched patients from each group, we identified 20.6 ± 7.2 LNs using the fat dissolution method compared to 13.5 ± 5.9 using the conventional method (t test, P < 0.01). Three patients in the FD group received an inappropriate LN examination in terms of number, while the number of the retrieved LNs was < 12 in 12 patients in the control group. The mean diameter of LNs without metastasis was 3.2 ± 1.9 mm in the FD group, and 40% of metastasis cases were found in LNs < 5 mm in diameter. A pathological examination confirmed that using the fat resolution method did not change the morphological or immunochemical staining findings. CONCLUSION: We demonstrated that fat dissolution had a positive impact on the number of retrieved LNs after colorectal cancer surgery without disturbing the microscopic observation.

Successful Laparoscopy-Assisted Resection of the Descending Colon in a Patient with Multiple Large Renal Cysts and Stricture of the Colon due to Ischemic Colitis.

Large pathological structures in the abdominal cavity curb the application of laparoscopic surgery. This case report describes a successful laparoscopy-assisted colectomy for benign colon disease in a patient with multiple large renal cysts. An 82-year-old man was referred to our department for treatment of stenosis of descending colon secondary to ischemic colitis. An abdominal computed tomography revealed multiple large renal cysts occupying a large proportion of the peritoneal cavity. To minimize the postoperative recovery period, laparoscopic surgery was planned despite the renal cysts. After inserting access ports, the walls of the several renal cysts were fenestrated with an electronic scalpel and the serous fluid was aspirated to enable continuation of the laparoscopic colectomy. The left colon was mobilized and extracted through an incision at the umbilicus, and the affected part of the colon was resected safely. The patient's postoperative course was uneventful, and the present case suggests that laparoscopy-assisted colectomy can be performed safely even in patients with multiple large renal cysts.

Lymph node retrieval after dissolution of surrounding adipose tissue for pathological examination of colorectal cancer.

Examination of >12 lymph nodes (LNs) is important for the diagnostic accuracy of nodal status following resection of colorectal cancer. In the present study, the efficacy of a fat dissolution technique for LN retrieval was evaluated using resected colon and rectum mesentery. First, the resected mesentery was searched for LNs by inspection and palpation immediately after surgery. Subsequently, fat dissolution liquid was applied to the remnant fat and the LN search was repeated. The primary endpoint was whether the second assessment would increase the number of evaluated LNs. Recruitment of 20 patients was planned. The study was conducted after institutional review board approval and written informed consent was obtained. Among 20 participants, 1 patient was excluded because LN dissection was not performed. The median number of LNs identified at the first and second assessments was 13 and 6, respectively, producing a significant increase in total LNs evaluated (13 vs. 20, respectively; P<0.01; paired t-test). One positive node was identified among the additionally identified LNs (0.9%, 1/107). The second assessment increased the number of LNs assessed to >12 in 4 patients, and although staging was not changed, the treatment was potentially altered in 2 stage II patients. The maximum diameter of the additionally obtained LNs was significantly smaller compared with those from the first assessment (4 vs. 7.7 mm, respectively; P<0.01; Wilcoxon signed-rank test). After the fat dissolution technique, the tumor cells were satisfactorily stained by carcinoembryonic antigen and cytokeratin-20. In conclusion, applying fat dissolution liquid to the remnant adipose tissue of the mesentery of the colon and rectum identified additional LNs. This method should be considered when insufficient LNs are identified after conventional LN retrieval.

Factors influencing the number of retrieved lymph nodes after colorectal resection: a retrospective study from a single institute.

Accurate diagnosis of lymph node (LN) metastasis is important to determine the staging and consequent treatment of resected colorectal cancer. Therefore, factors influencing the number of retrieved LNs were explored. This study included 400 patients that underwent surgical resection for Stage 0-III colorectal cancer from 2009 to 2014 in Kochi Medical School. In all cases, surgeons retrieved the LNs within the resected mesentery immediately after the operation without fixation. Age, gender, body mass index (BMI), American Association Anesthesiologist (ASA) scores, tumor locations, maximum tumor diameters, nodal status, and pathological tumor types were extracted as patient and tumor factors. The extent of LN dissection and surgical approaches (laparoscopic or laparotomy) were extracted as operative factors. Multivariate regression analysis was performed to identify independent predictive factors for LN number retrieved, after potential influential factors were explored by univariate analysis. As results, we found that the median number of retrieved LNs was 13, ranging from 1 to 50. Approximately 60% of the patients thus received an adequate examination (LN number of 12 or more). Multivariate analysis using the remaining factors of univariate analysis identified BMI, tumor diameter, nodal status, and extent of dissection as independent predictive factors for the number of retrieved LNs (P < 0.05). If any or all these factors are present, a vigorous search for LNs using additional measures, such as visual enhancement and fat dissolution method, should be considered.

Safety of laparoscopic surgery for colorectal cancer in patients over 80 years old: a propensity score matching study.

PURPOSES: To establish the safety of laparoscopic-assisted colorectal resection for colorectal cancer in elderly patients aged ≥80 years. METHODS: Data were obtained from a chart review of patients who underwent colorectal cancer resection between 2009 and 2014 in Kochi Medical School. The effect of patient age on the extent of lymph node dissection and operative safety was assessed by comparing the short-term results of elderly patients with those of younger patients after propensity score matching. RESULTS: Of a total of 506 patients with colorectal cancer, 398 underwent laparoscopic surgery and 23% of these patients were aged ≥80 years old. The elderly patients tended to have poorer general condition and larger tumors, although no significant differences were found in tumor invasion, lymph node metastasis, or synchronous distant metastasis between the groups. After adjustment for preoperative factors, we noted that the elderly patients tended to undergo less aggressive surgical resection (P = 0.01). Further analysis after including surgical factors for propensity score matching revealed a similar rate of complications in the two groups (24 vs. 25%, respectively; P = 0.85), and similar postoperative death rates and length of postoperative hospital stay. CONCLUSION: The findings of the present study demonstrate that laparoscopic surgery for colorectal cancer should not be avoided based on simply the age of the patient.

Current topics in glycemic control by wearable artificial pancreas or bedside artificial pancreas with closed-loop system.

The incidence of diabetes is increasing at an unprecedented pace and has become a serious health concern worldwide during the last two decades. Despite this, adequate glycemic control using an artificial pancreas has not been established, although the 21st century has seen rapid developments in this area. Herein, we review current topics in glycemic control for both the wearable artificial pancreas for type 1 and type 2 diabetic patients and the bedside artificial pancreas for surgical diabetic patients. In type 1 diabetic patients, nocturnal hypoglycemia associated with insulin therapy remains a serious problem that could be addressed by the recent development of a wearable artificial pancreas. This smart phone-like device, comprising a real-time, continuous glucose monitoring system and insulin pump system, could potentially significantly reduce nocturnal hypoglycemia compared with conventional glycemic control. Of particular interest in this space are the recent inventions of a low-glucose suspend feature in the portable systems that automatically stops insulin delivery 2 h following a glucose sensor value <70 mg/dL and a bio-hormonal pump system consisting of insulin and glucagon pumps. Perioperative tight glycemic control using a bedside artificial pancreas with the closed-loop system has also proved safe and effective for not only avoiding hypoglycemia, but also for reducing blood glucose level variability resulting in good surgical outcomes. We hope that a more sophisticated artificial pancreas with closed-loop system will now be taken up for routine use worldwide, providing enormous relief for patients suffering from uncontrolled hyperglycemia, hypoglycemia, and/or variability in blood glucose concentrations.

Re-evaluation of hepatocyte replacement by recipient-derived cells after allogenic liver transplantation: Discrepancy between clinical observations and a rat model.

AIM: Reports suggest that hepatocyte replacement by recipient-derived cells is an active phenomenon after allogenic liver transplantation in rats. However, this phenomenon is rarely observed in humans, and further evaluation is necessary to bridge the gap between clinical practice and animal experiment. METHODS: Fifty percent volume of the liver from green fluorescent protein (GFP) transgenic Lewis rats were transplanted into wild-type Dark Agouti (DA) rats, in which GFP negative hepatocytes were considered as host (DA rat)-derived cells. The transplanted liver was observed on whole imaging system and fluorescent microscope 7-10 days after transplantation. As a different method from previous reports, hepatocytes isolated from transplanted livers were cultured, and the expression of GFP was examined. RESULTS: The sliced liver (2 mm) after allogenic transplantation demonstrated decreased intensity of GFP signals compared with the positive control. The hematoxylin-eosin staining of the section revealed abundant infiltration of inflammatory cells, suggesting an immunological rejection reaction. Large polygonal cells with significantly decreased or negative GFP signals were also demonstrated, which was consistent with the results of previous studies. However, cell culturing demonstrated that none of the examined albumin positive large polygonal cells were host-derived cells. The same results were obtained irrespective of reconstruction of hepatic artery. CONCLUSION: Our result implies that rejection reaction does not promote parenchymal replacement by recipient-derived cells, in contrast to previous reports. If so, the phenomena occurring in rats are consistent with clinical observation of liver transplantation in humans.

[Two Cases of Krukenberg Tumors That Metastasized from Gastric Cancer Treated with Multidisciplinary Therapy].

A 34-year-old woman underwent total gastrectomy with D2 lymphadenectomy for gastric cancer, and the final diagnosis was T4N3M0, Stage III C, R0. Bilateral ovarian metastases were identified 51 months later, which were removed, and the patient received S-1 plus CDDP chemotherapy. Because the patient developed pubic bone metastasis 16 months after the second operation, we continued chemotherapy using paclitaxel with bisphosphonate. The patient was alive 70 months after the initial operation. The second patient was a 55-year-old woman who underwent total gastrectomy with D2 lymphadenectomy and was diagnosed with T2N2M0, Stage III A gastric cancer. Bilateral ovarian metastases were identified 72 months later, which were removed, and the patient received S-1 plus CDDP chemotherapy. The patient is alive with no signs of disease recurrence 96 months after the initial operation. For patients with ovarian metastases from gastric cancer, surgical resection in addition to chemotherapy might be an effective treatment. However, further studies and assessments of additional cases are needed to confirm the ideal treatment for this condition.

Rarity of late anastomotic leakage after low anterior resection of the rectum.

BACKGROUND: Late anastomotic leakage is reported to account for half of all anastomotic leakages after low anterior resection of the rectum. An important clinical question is whether late and early anastomotic leakages are different entities. METHODS: We retrospectively reviewed the medical records of patients who experienced anastomotic leakage after low anterior resection in two Japanese hospitals. The clinical characteristics were extracted and analyzed. RESULTS: During the study period, 179 patients underwent low anterior resection. A pelvic drainage tube was routinely utilized in all cases and was generally removed 4 to 6 days after the operation. Twenty-six patients had anastomotic leakage; the diagnosis was based on fecal contamination of the drainage in 24 cases. The median interval between operation and detection of anastomotic leakage was 3.5 days. Anastomotic leakage was diagnosed within 7 days of the operation in 25 cases and on postoperative day 20 (after hospital discharge) in one case. There was no instance of anastomotic leakage diagnosed more than 30 days after the operation. There was no relationship between clinical variables and days of leakage diagnosis. CONCLUSION: The rarity of late anastomotic leakage in our study, compared with previous studies, may relate to the relatively extended period of pelvic drainage tube usage in our institutes, which likely shortens the interval before leakage diagnosis. Our results suggest that late anastomotic leakage is a delayed symptom of subtle early anastomotic leakage rather than a separate entity.

Cetuximab and panitumumab in a patient with colon cancer and concomitant chronic skin disease: a potential beneficial effect on psoriasis vulgaris.

Monoclonal antibodies against epidermal growth factor receptor (EGFR) are used in the treatment of advanced colorectal cancer. However, these agents can induce severe dermatological side effects that discourage their administration in patients with chronic dermatological disease. EGFR plays a key role in normal skin development and immunological function, and is expressed in various tissues and organs, although contrarily, it is overexpressed in psoriasis-related skin lesions. Thus, discussion is ongoing regarding the putative pathological role and therapeutic potential of this protein. We herein report on a patient with advanced colon cancer and concomitant long-standing psoriasis vulgaris who received anti-EGFR antibody monotherapy as a third-line treatment for metastatic disease. One week after the initiation of treatment, the patient's skin lesions dramatically subsided and the improvement was sustained during therapy. Based on this case, we propose that anti-EGFR antibody therapy is not necessarily contraindicated in patients with psoriasis vulgaris. Moreover, the findings reaffirmed that EGFR is an important molecule in the pathology of psoriasis.

[The Clinical Role of the Neutrophil/Lymphocyte Ratio in Patients with Advanced Gastric Cancer Treated with Protein-Bound Polysaccharide K and Chemotherapy].

This study aimed to evaluate the efficacy of protein-bound polysaccharide K (PSK)-containing chemotherapy in patients with unresectable advanced or recurrent gastric cancer (AGC). We retrospectively analyzed 190 patients with AGC who received systemic chemotherapy including 69 patients who were treated with a PSK-containing regimen. Using propensity score matching, we obtained 62 matched patients in the S-1 and S-1 plus PSK groups for outcomes analysis. There was a tendency for overall survival to be higher in the S-1 plus PSK group than in the S-1 alone group. In particular, there was a tendency for overall survival in the S-1 plus PSK group to be higher in patients with a neutrophil/lymphocyte ratio (NLR)<2.2 than in patients with a NLR<2.2. There was a tendency for fewer changes in the NLR after the beginning of treatment in the S-1 plus PSK group than in the S-1 alone group. PSK-containing chemotherapy may contribute to improved treatment outcomes of AGC patients. In particular, it may be effective in patients with a high NLR. Further investigations, including a prospective randomized controlled trial, are expected to verify the mechanisms of interaction between cancer cells and the immunoreaction.

Nodular fasciitis in the mesentery, a differential diagnosis of peritoneal carcinomatosis.

Nodular fasciitis is a benign proliferative lesion composed of fibroblast-like cells that affects various sites in the body. We describe a patient with nodular fasciitis in the mesentery, encountered during laparotomy for the treatment of ascending colon cancer. The nodular fasciitis in our patient resembled peritoneal dissemination of malignancy on macroscopic observation. Because the treatment options change with concomitant peritoneal dissemination of gastrointestinal tract malignancy, recognition of this rare condition and preparation for unexpected nodular lesions are crucial.

Photodynamic diagnosis using 5-aminolevulinic acid during gastrectomy for gastric cancer.

BACKGROUND AND OBJECTIVES: Five-aminolevulinic acid (ALA) has received much attention recently as a new-generation photosensitive substance for photodynamic diagnosis (PDD). This study aimed to investigate the feasibility of intraoperative PDD using ALA to identify gastric cancer. METHODS: Intraoperative PDD was carried out in 26 lesions of 21 patients with gastric cancer. Before surgery, 1.0 g of ALA solution was given orally through a stomach tube. After tumor resection, resected specimens were investigated by an endoscopic PDD system, and red fluorescence-positive lesions were compared with the pathological result. RESULTS: Red fluorescence was detected in 15 lesions of 11 patients. The sensitivity, specificity, and accuracy of PDD using ALA in detecting gastric cancer were 57.7, 100, and 66.7%, respectively. The incidence of laparoscopic surgery was significantly lower in the PDD-positive group than in PDD-negative cases (18.2% vs. 60.0%; P = 0.049), while that of intestinal type tumor was significantly higher in PDD-positive compared to PDD-negative patients (93.3% vs. 27.3%; P < 0.001). CONCLUSIONS: Fluorescence navigation by PDD provides good visualization and detection of gastric cancer lesions, and might be particularly useful for intestinal type gastric cancer. Thus, PDD using ALA seems to be a promising diagnostic tool for gastric cancer.

[A case of gastric cancer with solitary metachronous adrenal metastasis].

A 61 -year-old man underwent total gastrectomy with distal pancreatectomy and D2 lymphadenectomy for gastric cancer. The final diagnosis was UM, Post-Gre-Less, Type 3, 12 × 9 cm, T4b (SI), N3b (31/99), H0, P0, CY0, M0, tub2, ly3, v3, Stage IIIC, R0. Fifteen months after the operation, abdominal computed tomography showed a left adrenal tumor measuring 2.5 cm in diameter. Because it was a solitary tumor, we performed tumor resection, confirming adrenal metastasis that was negative for human epidermal growth factor receptor type 2 (HER2). Subsequently, the patient was treated with a chemotherapy regimen consisting of S-1 plus cisplatin. Because he developed left adrenal metastasis 6 months after tumor resection, we initiated chemotherapy with docetaxel plus irinotecan. Left adrenalectomy was performed owing to the tumor increasing to 3.6 cm despite chemotherapy. The patient is currently alive 50 months after the initial operation, without any signs of disease recurrence. For patients with solitary adrenal metastasis from gastric cancer, surgical resection in addition to chemotherapy might be the preferred choice of treatment.

[Efficacy of trastuzumab-containing regimens in patients with unresectable advanced or recurrent gastric cancer].

In the present study, we aimed to evaluate the efficacy and safety of trastuzumab-containing regimens in patients with unresectable advanced or recurrent gastric cancer( AGC). We retrospectively analyzed 142 patients with AGC who received systemic chemotherapy, including 10 patients treated with trastuzumab-containing regimens. Among the 72 patients, 12 (16.7)% were human epidermal growth factor receptor 2 (HER2)-positive; the HER2-positive rate was significantly greater in patients with intestinal-type than diffuse-type histology( 29.0 vs 7.3%; p=0.014). The median overall survival of patients treated with trastuzumab was significantly longer than that of patients treated without trastuzumab( 22.9 vs 11.6 months; p =0.014). Seven patients continued receiving trastuzumab therapy after disease progression, and 6 patients were treated with trastuzumab after initial chemotherapy. The objective response rate of trastuzumab-containing regimens was 40%. The frequency of hematological and non-hematological toxicities was feasible. The administration of trastuzumab therapy after disease progression may contribute to improved treatment outcomes. However, further investigations, including prospective randomized controlled trials, are needed to verify this finding.

Metachronous liver and bone metastasis from small early gastric carcinoma without lymph node involvement: A case report.

A 65-year-old man was referred to our Hospital for examination of gastric cancer initially diagnosed by medical check-up. Esophagogastroduodenoscopy demonstrated a superficial depressed-type gastric cancer in the antrum, and abdominal computed tomography showed no evidence of distant metastases. A tumor measuring 11 mm in diameter was removed by endoscopic submucosal dissection (ESD). Since histological examinations of ESD specimens showed a well-differentiated adenocarcinoma invading the submucosal layer with lymphatic invasion, the patient subsequently underwent laparoscopy-assisted distal gastrectomy with regional lymph node dissection, resulting in no residual carcinoma and no lymph node metastasis. The patient developed solitary liver metastasis one year later and was treated with trastuzumab plus capecitabine/cisplatin since results of the immunohistochemical analysis of the resected specimens demonstrated overexpression of the human epidermal growth factor receptor 2 (HER2). The patient was alive 12 months after surgical resection of the liver metastasis and subsequently developed bone metastasis. Controversy remains over the role of HER2 status as a prognostic factor in gastric cancer. However, it has been generally reported that HER2 overexpression correlates with aggressive biological behavior and poor prognosis. HER2 overexpression is a potentially useful predictive factor for tumor recurrence and poor prognosis even in early gastric cancer cases.

The effect of the neutrophil elastase inhibitor sivelestat on early injury after liver resection.

BACKGROUND: The effects of sivelestat on endotoxin-induced lung injury, postperfusion lung injury, and ischemia-reperfusion are known, yet the benefits of sivelestat during liver surgery have yet to be elucidated. The aim of the present study was to assess the effects of sivelestat, with a focus on postoperative chemical data, in hepatectomized patients. PATIENTS AND METHODS: A prospective clinical study was conducted in 50 patients undergoing hepatic resection. Patients were randomly assigned to receive Elaspol, sivelestat (ELP group, n = 25) or placebo (control group, n = 25). Perioperative blood chemistry values in both groups, including high-mobility group box 1 (HMGB1) and interleukin (IL)-6, were monitored. RESULTS: The HMGB1 levels increased immediately after the operation (from the intraoperative period to the second postoperative day [POD]) in the control group. Compared to the control group, the levels of HMGB1 in the ELP group were significantly suppressed by the perioperative administration of sivelestat. At POD 1, the levels of IL-6 in the ELP group decreased more rapidly than those before the operation compared to the control group. CONCLUSIONS: A human clinical study demonstrated the effect of polymorphonuclear leukocyte elastase inhibitor on the earliest markers of liver injury. The present study showed that patients who received sivelestat had reduced release of HMGB1, and that IL-6 levels decreased more rapidly in patients treated with sivelestat than in those who received the placebo. The most appropriate dose, timing, and duration of sivelestat in humans remain unclear; however, it may have therapeutic potential for various liver injuries.