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.

Evaluation of Perioperative Intestinal Motility Using a Newly Developed Real-Time Monitoring System During Surgery.

BACKGROUND: This study aimed to investigate perioperative intestinal motility using a novel bowel sound monitoring system in patients undergoing breast and neck surgery. MATERIALS AND METHODS: This study enrolled 52 patients who underwent surgery for breast cancer, thyroid tumor, and parathyroid tumor at Kochi Medical School from May 2019 to June 2020. Perioperative bowel sound counts (BSCs) were recorded using a newly developed real-time analysis system in the operating theater. Clinical information and BSC per minute (cpm) data during the preanesthetic, preoperative, operative, postoperative periods, and period in recovery room were obtained to compare between each period. The Mann-Whitney U and Pearson Chi-square tests were used in data analysis. RESULTS: The BSCs during the intraoperative period and postoperative period were significantly decreased compared to those during the preanesthetic period (0.07 cpm versus [vs.]. 1.4 cpm, P = 0.002 and 0.1 cpm vs. 1.4 cpm, P = 0.025, respectively). The preoperative BSC with a preanesthetic BSC < 1.4 was significantly lower than that with a preanesthetic BSC ≥ 1.4 (0.40 cpm vs. 1.78 cpm, P = 0.006). The preanesthetic, preoperative, and postoperative BSCs with an intraoperative BSC < 0.07 were significantly lower than those with an intraoperative BSC ≥ 0.07 (0.48 cpm vs. 2.83 cpm, P = 0.007; 0.40 cpm vs. 1.81 cpm, P = 0.008; and 0.07 cpm vs. 0.42 cpm, P = 0.006, respectively). CONCLUSION: The real-time bowel sound analysis system demonstrated an inhibitory effect associated with anesthetic and surgical stress on intestinal motility as the BSC sequentially.

Evaluation of Follow-up Examinations Using Ultrasonography for Patients With Thyroid Nodules Initially Diagnosed as Benign.

BACKGROUND/AIM: The aim of this study was to determine the natural history of benign thyroid nodules using ultrasonography. PATIENTS AND METHODS: The records of 223 patients with benign thyroid nodules treated at the Kochi Medical School from 2010 to 2012 were reviewed retrospectively. Repeated ultrasonography was performed, and the findings were directly compared with previous images. RESULTS: The median change in the size of the nodules was 0.01 cm/year, although the size of six nodules (2.7%) increased more than 0.5 cm/year, and these nodules were removed surgically. Nineteen patients (8.5%) underwent surgery during the follow-up period. Compared to those who did not undergo surgery, the size of the nodules was larger and the rate of change in nodule diameter was higher in those undergoing surgery. The pathological diagnosis based on repeated fine needle aspiration cytology was benign nodules in 16 patients and papillary cancer in three patients. CONCLUSION: Even if a thyroid nodule is initially diagnosed as benign, it may have malignant potential. Therefore, so as not to miss malignancies, nodules should be carefully re-evaluated to assess their growth or change in size using ultrasonography.

[A Case of Early-Onset Breast Cancer for Which the Operative Indication for Breast Conservation Was Based on BRCA Genetic Testing].

We report a case of a patient with early-onset breast cancer who decided to undergo adaptation for breast-conserving surgery based on the results of genetic testing. A 25-year-old woman became aware of a lump in her left breast and visited a nearby hospital, where she was diagnosed with breast cancer. She has no personal history. Her paternal grandfather was diagnosed with rectal cancer at age 60. Ultrasonography revealed an irregularly-shaped hypoechoic mass measuring 3.8 cm in the C area of her left breast and an enlarged lymph node 2.0 cm in diameter in the left axillary area. The breast tumor was pathologically diagnosed as invasive ductal carcinoma by core needle biopsy and was immunohistochemically characterized as ER(-), PgR(-), and HER2(-), s o-called triple negative. Moreover, lymph node metastasis was confirmed by fine needle aspiration cytology. She underwent neoadjuvant chemotherapy and achieved a clinical complete response. A woman with early-onset triple negative breast cancer has a high probability of hereditary breast and ovarian cancer, with a high risk of ipsilateral second breast cancer after conserving surgery. Thus, BRCA genetic testing may be necessary before surgery. As no pathogenic mutation wasfound in BRCA 1/2 in this case, the patient underwent breast-conserving surgery followed by radiation therapy for the conserved breast. The patient remained healthy and without any recurrence 4 years and 2 months after surgery.

Gastric outlet obstruction caused by metastatic tumor of the stomach originating from primary breast cancer: A case report.

The most common sites of breast cancer metastasis are the bone, liver, lung and brain, while gastrointestinal metastasis from breast cancer is rare. We herein present the case of a 68-year-old woman who was admitted to our department with nausea and appetite loss. The patient's medical history included right mastectomy with sentinel lymph node biopsy 5 years earlier for invasive lobular carcinoma, measuring 6.2 cm in greatest diameter, without lymphovascular invasion. Two years after the surgery, the patient developed brain metastasis and underwent metastasectomy to control the neurological symptoms, including unsteadiness and asthenia. After the second surgery, the patient received systemic chemotherapy using S-1, followed by bevacizumab plus paclitaxel. However, due to bevacizumab-related cardiotoxicity, the treatment was switched to eribulin. On esophagogastroduodenoscopy, an elevated lesion was identified in the antrum, causing severe narrowing of the gastric outlet. Biopsy and histological examination of the tumor revealed infiltration of the gastric wall by undifferentiated neoplastic cells with poor adhesion, morphologically similar to invasive lobular carcinoma, and immunohistochemical staining was positive for estrogen receptor, mammaglobin and GATA3. Finally, 18F-2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography combined with computed tomography imaging revealed FDG uptake across the thickness of the antral wall. The patient was diagnosed with gastric metastasis from the original breast cancer and subsequently underwent endoscopic self-expandable metallic stent (SEMS) placement. There were no procedure-related adverse events, and the patient remained alive under best supportive care 4 months after SEMS placement. To the best of our knowledge, this is the first reported case of gastric outlet obstruction caused by metastatic breast carcinoma managed by SEMS placement. While such a diagnosis is rare, clinicians treating patients with gastric metastases should be aware of possible gastric outlet obstruction and SEMS placement as an effective palliative intervention.

BCL7B, a predictor of poor prognosis of pancreatic cancers, promotes cell motility and invasion by influencing CREB signaling.

The functions of B-cell CLL/lymphoma 7B (BCL7B) are unknown and the protein lacks any known functional domains. The aim of this study was to investigate the role of BCL7B in the motility and invasiveness of pancreatic cancer cells. Immunohistochemistry was performed to determine whether high BCL7B expression in human pancreatic cancer tissues is correlated with poor prognosis. High BCL7B expression was an independent predictor of worse overall survival of pancreatic cancer patients. Immunocytochemistry showed that BCL7B was accumulated in cell protrusions of migrating pancreatic cancer cells. Knockdown of BCL7B inhibited the motility and invasiveness of pancreatic cancer cells through a decrease in cell protrusions. Phosphoprotein array analysis was performed to determine BCL7B-associated intracellular signaling pathways. Suppression of BCL7B increased phosphorylated CREB expression in pancreatic cancer cells, and knockdown of CREB promoted the motility and invasiveness by increasing cell protrusions. The combined data suggest that BCL7B promotes pancreatic cancer cell motility and invasion through a signaling pathway that involves dephosphorylation of CREB.

CCDC88A, a prognostic factor for human pancreatic cancers, promotes the motility and invasiveness of pancreatic cancer cells.

BACKGROUND: Coiled-Coil Domain Containing 88A (CCDC88A) was identified as a substrate of the serine/threonine kinase Akt that is capable of binding to the actin cytoskeleton. The aim of this study was to investigate the potential role of CCDC88A in the migration and invasiveness of pancreatic ductal adenocarcinoma (PDAC) cells. METHODS: Immunohistochemistry was performed to determine whether high CCDC88A expression in human PDAC tissues is correlated with poor prognosis. Immunoprecipitation, immunoblotting and immunocytochemistry were performed to determine the intracellular distribution of CCDC88A, and its association with the serine/threonine kinase Akt and actin-filaments in PDAC cells. Phosphoprotein array analysis was performed to determine CCDC88A-associated intracellular signaling pathways. Finally, immunofluorescence analyses and Matrigel invasion assays were performed to examine the effects of CCDC88A on the formation of cell protrusions and PDAC cell invasion. RESULTS: Expression of CCDC88A in PDAC tissue was significantly correlated with overall survival. CCDC88A was co-localized with peripheral actin structures in cell protrusions of migrating PDAC cells. Knockdown of CCDC88A inhibited the migration and invasiveness of PDAC cells through a decrease in cell protrusions. Although CCDC88A has been previously reported to be a binding partner and substrate of Akt, the level of active Akt was not associated with the translocation of CCDC88A towards cell protrusions. CCDC88A-dependent promotion of cell migration and invasiveness was not modulated by Akt signaling. Knockdown of CCDC88A decreased phosphorylated Src and ERK1/2 and increased phosphorylated AMPK1 in PDAC cells. Knockdown of AMPK1 inhibited the migration and invasiveness of PDAC cells. The combined data suggest that CCDC88A may be a useful marker for predicting the outcome of patients with PDAC and that CCDC88A can promote PDAC cell migration and invasion through a signaling pathway that involves phosphorylation of Src and ERK1/2 and/or dephosphorylation of AMPK1. CONCLUSIONS: CCDC88A was accumulated in cell protrusions, contributed to the formation of membrane protrusions, and increased the migration and invasiveness of PDAC cells.

Vav3 is linked to poor prognosis of pancreatic cancers and promotes the motility and invasiveness of pancreatic cancer cells.

BACKGROUND/OBJECTIVES: The aim of this study was to investigate the role of the guanine nucleotide exchange factor Vav3 in the motility and invasiveness of pancreatic ductal adenocarcinoma (PDAC) cells. METHODS: Immunohistochemistry was used to determine whether high Vav3 expression in human PDAC tissues is correlated with poor prognosis. Immunocytochemistry was used to determine the association and intracellular distribution of Vav3, Rac1 and Akt in PDAC cells. Phosphoprotein array analysis was performed to determine the Vav3-associated intracellular signaling pathways. Immunocytochemistry and Matrigel invasion assays were used to examine the effects of Vav3 on the formation of cell protrusions and PDAC cell invasion. RESULTS: Expression of Vav3 in PDAC tissue was significantly correlated with overall survival. Vav3 was localized in cell protrusions of migrating PDAC cells. Knockdown of Vav3 inhibited the motility and invasiveness of PDAC cells through a decrease in cell protrusions. The levels of active Rac1 or active Akt were not associated with the concentration of Vav3 in cell protrusions. The Vav3-dependent promotion of motility and invasiveness was not modulated by Rac1 or Akt. Additionally, knockdown of Vav3 increased phosphorylated WNK1 in PDAC cells, and knockdown of WNK1 inhibited the motility and invasiveness. This study suggests that Vav3 can be a useful marker for predicting the outcome of patients with PDAC and that Vav3 can promote PDAC cell motility and invasion through association with dephosphorylation of WNK1. CONCLUSIONS: Vav3 was accumulated in cell protrusions, contributed to the formation of membrane protrusions, and thereby increased the motility and invasiveness of PDAC cells.

Podocalyxin-like protein, linked to poor prognosis of pancreatic cancers, promotes cell invasion by binding to gelsolin.

The cell-adhesion glycoprotein PODXL is associated with an aggressive tumor phenotype in several forms of cancer. Here, we report that high PODXL expression was an independent predictor of worse overall survival of pancreatic cancer patients, and that PODXL promoted pancreatic cancer cell motility and invasion by physically binding to the cytoskeletal protein gelsolin. Suppression of PODXL or gelsolin decreased membrane protrusions with abundant peripheral actin structures, and in turn inhibited cell motility and invasion. Transfection of a PODXL-rescue construct renewed the expression of gelsolin bound to peripheral actin structures in cell protrusions, and abrogated the decreased cell protrusions caused by the knockdown of PODXL. Furthermore, transfection of a PODXL-rescue construct into pancreatic cancer cells in which both PODXL and gelsolin were suppressed failed to increase the formation of the protrusions. Thus, PODXL enhances motility and invasiveness through an increase in gelsolin-actin interactions in cell protrusions.

Evaluation of the minimally invasive parathyroidectomy in patients with primary hyperparathyroidism: A retrospective cohort study.

INTRODUCTION: An accurate differential diagnosis between single adenoma (SA) and multiglandular disease (MGD) remains difficult in Technetium-99m sestamibi scintigraphy (MIBI)-negative patients with primary hyperparathyroidism (PHPT). The aim of the present study was to evaluate the minimally invasive parathyroidectomy (MIP) in patients with PHPT. METHODS: Clinical records of 48 patients who underwent neck exploration between November 2002 and June 2012 in Kochi Medical School Hospital were reviewed retrospectively to identify candidates that underwent for MIP which was defined as the selective removal of a SA using less invasive surgery. RESULTS: The preoperative detection rate of lesions using ultrasonography, MIBI, computed tomography, and magnetic resonance imaging was 90%, 83%, 76%, and 55%, respectively. Although all 39 patients in the MIBI-positive group were diagnosed with an SA and subsequently underwent curative MIP, 3 patients in MIBI-negative group (n = 6) were MGD, who underwent neck exploration. Preoperative mean intact parathyroid hormone (419 pg/ml vs. 149 pg/ml; P < 0.01) and alkaline phosphatase levels (746 U/l vs. 277 U/l; P < 0.01) were significantly higher in the SA than MGD group. CONCLUSIONS: In MIBI-negative patients with indications for surgery, MIP should not be carried out without a clear localization of SA, or in MGD.

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.

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.

Perioperative intensive insulin therapy using an artificial endocrine pancreas with closed-loop glycemic control system: the effects of no hypoglycemia.

BACKGROUND: We examined whether perioperative intensive insulin therapy (IIT) using an artificial pancreas (AP) with a closed-loop glycemic control system can be used to prevent hypoglycemia in surgical patients. METHODS: Between 2006 and 2012, perioperative glycemic control using an AP was performed in 427 patients undergoing general surgery. A total of 305 patients undergoing IIT using an AP in the target blood glucose range of 80 to 110 mg/dL were enrolled in the study. Data were collected prospectively and were reviewed or analyzed retrospectively. RESULTS: No patients had hypoglycemia. Perioperative mean blood glucose level and achievement rates in target blood glucose range of 80 to 110 mg/dL were 100.5 ± 11.9 mg/dL and 88.1% ± 16.0%, respectively. For the 3 primary operative methods, including hepatic, pancreatic, and esophageal resections, there were no significant differences in glycemic control stability between the types of surgery. CONCLUSION: Perioperative IIT using an AP with a closed-loop glycemic control system can be used to prevent hypoglycemia and maintain stable glycemic control with less variability of blood glucose concentration.

Diamine oxidase as a marker of intestinal mucosal injury and the effect of soluble dietary fiber on gastrointestinal tract toxicity after intravenous 5-fluorouracil treatment in rats.

The level of plasma diamine oxidase (DAO) activity is associated with the maturation and integrity of small intestinal mucosa. This study in rats investigated whether a decreased level of plasma DAO could reflect the severity of mucosal injury due to intravenous 5-fluorouracil (5-FU) treatment. The beneficial effect of soluble dietary fiber (SDF) on preventing diarrhea after 5-FU treatment was also examined. To induce diarrhea, 5-FU (50 mg/kg/day for four days) was administered via the tail vein with or without SDF supplementation. After 5-FU treatment, the majority of rats developed moderate to severe diarrhea, and levels of plasma DAO activity significantly decreased compared to those of control group (P < 0.05). Scanning electron microscopy revealed disarrangement of the small intestinal villi. Contrarily, the rats supplemented with SDF had diarrhea less frequently (50.0 vs. 91.7 %, P = 0.025) on day five, and DAO activity levels were significantly higher than in those rats administered 5-FU alone (8.25 ± 5.34 vs. 5.50 ± 4.32, P = 0.023). In conclusion, plasma DAO activity decreases in response to severe intestinal mucosal injury after 5-FU treatment, and SDF supplementation might be a practical and useful treatment for reducing the intestinal toxicity of 5-FU.

Effect of Daikenchuto (TJ-100) on abdominal bloating in hepatectomized patients.

AIM: To evaluate the clinical usefulness of Daikenchuto (DKT) in hepatecomized patients. METHODS: Twenty patients were enrolled with informed consent. Two patients were excluded because of cancelled operations. The remaining 18 patients were randomly chosen for treatment with DKT alone or combination therapy of DKT and lactulose (n = 9, each group). Data were prospectively collected. Primary end points were Visual Analogue Scale (VAS) score for abdominal bloating, total Gastrointestinal Symptoms Rating Scale (GSRS) score for abdominal symptoms, and GSRS score for abdominal bloating. RESULTS: The VAS score for abdominal bloating and total GSRS score for abdominal symptoms recovered to levels that were not significantly different to preoperative levels by 10 d postoperation. Combination therapy of DKT and lactulose was associated with a significantly poorer outcome in terms of VAS and GSRS scores for abdominal bloating, total GSRS score, and total daily calorie intake, when compared with DKT alone therapy. CONCLUSION: DKT is a potentially effective drug for postoperative management of hepatectomized patients, not only to ameliorate abdominal bloating, but also to promote nutritional support by increasing postoperative dietary intake.

[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.