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).

Theoretical studies of diverse sexual patterns in marine animals.

Marine animals show diverse and flexible sexual systems. Here, we review several advancements of theoretical studies made in the last decade. (i) Sex change in coral fishes is often accompanied by a long break in reproductive activity. The delay can be shortened by retaining the inactive gonad for the opposite sex. (ii) Barnacles adopt diverse sexual patterns. The game model was analysed assuming that newly settled larvae choose either growth or immediate reproduction and large individuals adjust male-female investments. (iii) Some parasitic barnacles produce larvae with sexual size dimorphism and others produce larvae with the sex determined after settlement on hosts. (iv) In some fish and many reptiles, sex is determined by the temperature experienced as eggs. The dynamics of sex hormones were studied when the enzymatic reaction rates were followed by the Arrhenius equation. The FMF pattern (male at intermediates temperature; female both at high and low temperatures) required some reactions with enhanced temperature dependence at higher temperatures. The game model provides a useful framework for understanding diverse sexual patterns if we incorporate various constraints, such as unpredictability, cost of trait change and social situations. For further developments, we need to consider constraints imposed by physiological and molecular mechanisms.

[Long-Term Survival of an Adolescent and Young Adult Patient with Unresectable Advanced Gastric Cancer in Whom Multidisciplinary Treatment Was Effective].

We report the case of a long-term-surviving adolescent and young adult patient with unresectable advanced gastric cancer for whom multidisciplinary treatment was effective. A 29-year-old woman was referred to our hospital for further examination following a diagnosis of gastric cancer by a local physician. Esophagogastroduodenoscopy showed a deep ulcerated lesion in the lower third of the stomach, and analysis of biopsy specimens revealed an adenocarcinoma. Abdominal contrast- enhanced computed tomography showed gastric wall thickening in the lower third of the stomach. The patient underwent distal gastrectomy with lymph node dissection, including resection of localized peritoneal metastases, followed by Roux-en- Y reconstruction. The pathological diagnosis was serosa-invading poorly differentiated adenocarcinoma with 1 lymph node metastasis measuring 6.0×5.5 cm in the posterior wall of the lower third of the stomach and negative immunohistochemical staining for human epidermal growth factor receptor 2. The patient received postoperative chemotherapy with S-1 and oxaliplatin. She developed bilateral ovarian metastases measuring 13.0 cm and 7.8 cm after 17 months. The patient presented with severe lower abdominal pain and underwent an emergency bilateral ovarian metastasectomy, which revealed torsion of the right ovarian tumor, which had twisted twice on its pedicle, and a left ovarian mass. After the operation, 41 courses of ramucirumab with nab-paclitaxel were administered as a second-line treatment, and she received systemic drug treatment. Sixty months after the gastrectomy, the patient developed left hydronephrosis due to peritoneal metastases and was treated with nivolumab after ureteral stent replacement. No effective treatment was proposed in cancer multigene panel testing, and she died 66 months after the initial treatment because of disease progression. Comprehensive multidisciplinary treatment, including surgical and local therapy for peritoneal dissemination based on drug therapy for unresectable advanced gastric cancer, may result in long-term survival. Further research and accumulation of such cases would lead to the development of novel treatments.

Successful conversion surgery after FOLFIRINOX therapy in a patient with advanced pancreatic acinar cell carcinoma with a solitary peritoneal dissemination: A case report.

BACKGROUND: Pancreatic acinar cell carcinoma is rare; it accounts for 1% of all malignant pancreatic exocrine tumors. Although surgical resection is an option for curative treatment, the safety and efficacy of conversion surgery in patients with pancreatic acinar cell carcinoma with metastasis remain unknown. CASE: A 67-year-old man with epigastric pain and a pancreatic tumor was referred to our hospital. Computed tomography revealed a large tumor with a maximum diameter of 67 mm at the pancreatic head and a 23-mm mass in the left upper abdominal cavity. Because a definitive diagnosis could not be made based on endoscopic ultrasonography-guided fine needle aspiration biopsy findings, a diagnostic laparoscopy was performed. The tumor in the greater omentum at the left upper abdomen, resected under laparoscopy, was histopathologically diagnosed as pancreatic acinar cell carcinoma. Therefore, the pancreatic tumor was diagnosed as an unresectable pancreatic acinar cell carcinoma with a solitary peritoneal dissemination. The size of the main pancreatic tumor decreased to 15 mm after 18 courses of FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin). Subsequently, the patient underwent conversion surgery, and the initial diagnosis of pancreatic acinar cell carcinoma was confirmed on pathological examination. The patient was discharged 31 days postoperatively, following which he received adjuvant chemotherapy with S-1. No sign of recurrence has been observed for 32 months after surgical resection. CONCLUSION: FOLFIRINOX may be effective in patients with pancreatic acinar cell carcinoma, and conversion surgery after FOLFIRINOX may be applicable to selective patients.

Primary Superior Lumbar Hernia with Nephrotic-range Orthostatic Proteinuria.

Lumbar hernias are extremely rare. The posterolateral abdominal wall has two susceptible areas - the superior (Grynfeltt-Lesshaft's triangle) and the inferior (Petit's triangle) lumbar triangles - that cause superior and inferior lumbar hernias, respectively. We herein report a 67-year-old woman with nephrotic-range proteinuria caused by primary superior lumbar hernia. Superior lumbar hernias should be considered as a differential disease causing massive orthostatic proteinuria in adults. The present case highlights the importance of considering lumbar hernia in patients with flank swelling and the potential complications that may result from a missed diagnosis.

Optimal composition of chloride cells for osmoregulation in a randomly fluctuating environment.

Fish live in water with a different osmotic pressure from that in the body. Their gills have chloride cells that transport ions to maintain an appropriate level of osmotic pressure in the body. The direction of ion transport is different between seawater and freshwater. There are two types of chloride cells that specialize in unidirectional transport and generalist cells that can switch their function quickly in response to environmental salinity. In species that experience salinity changes throughout life (euryhaline species), individuals may replace some chloride cells with cells of different types upon a sudden change in environmental salinity. In this paper, we develop a dynamic optimization model for the chloride cell composition of an individual living in an environment with randomly fluctuating salinity. The optimal solution is to minimize the sum of the workload of chloride cells in coping with the difference in osmotic pressure, the maintenance cost, and the temporal cost due to environmental change. The optimal fraction of generalist chloride cells increases with the frequency of salinity changes and the time needed for new cells to be fully functional but decreases with excess maintenance cost.

Evolutionary game of life-cycle types in marine benthic invertebrates: Feeding larvae versus nonfeeding larvae versus direct development.

Many marine invertebrates have a benthic adult life with planktonic long feeding larval stages (planktotrophy). In other species, planktonic larvae do not eat, and after a rather short period, they settle and initiate their benthic stages (lecithotrophy). Still other species skip planktonic larval stages altogether, and adults produce benthic offspring (direct development). In this paper, we develop an evolutionary game among different life-cycle types and examine the conditions for each life-cycle type to win in a seasonal environment. The growth rate and mortality of benthic individuals are the same among all three life-cycle types, the local habitat (patches) for benthic individuals have a finite longevity, and adults may engage in a limited dispersal just before breeding. Planktotrophy evolves if the planktonic stages are more efficient in terms of biomass gain than benthic life. Otherwise, lecithotrophy or direct development should evolve. Among them, direct development is more advantageous than lecithotrophy if the cost of having planktonic larvae is large, the habitat for benthic individuals is stable, and adults engage in some dispersal.

Evolution of male nuptial gift and female remating: A quantitative genetic model.

In some species of separate sexes, males present a nuptial gift containing nutrition to their mate. Producing a large nuptial gift is a considerable cost to the male, but it may improve his siring success if the female reduces the likelihood to accept another male after receiving a large gift. The female may receive a direct benefit by accepting another male who provides an additional nuptial gift. Additionally, the female may receive an indirect fitness benefit via laying offspring sired by a male who is able to produce a large nuptial gift. We formalized the multivariate quantitative genetics model describing the coevolution of the size of nuptial gift produced by the male (x) and the female's propensity to engage in remating (y). We analyzed the model focusing two cases: [1] remating females receive no indirect fitness benefit, but enjoy direct benefit of nutrition; and [2] remating females receive no direct benefit, but enjoy an indirect fitness benefit due to a positive genetic correlation of x and y, which is possible if random mutations tend to make males produce small nuptial gifts. In both cases, the stable evolutionary equilibrium with neither nuptial gift nor remating (x-=y-=0) always exists. Another stable equilibrium may exist in which male produces nuptial gifts (x->0) and female engage in multiple mating (y->0). We discussed implications to the sexual conflict.

Spontaneous intra-abdominal hemorrhage of a well-differentiated, grade 3 gastric neuroendocrine tumor during drug-based treatment.

Grade 3, well-differentiated, gastric neuroendocrine tumors (NET G3) are extremely rare. Herein, we report the case of a 64-year-old man with a grade 3 neuroendocrine tumor of the stomach who experienced intra-abdominal bleeding during the course of drug treatment. The patient was referred to our hospital for examination of a gastric tumor that was initially diagnosed by a local medical doctor. Esophagogastroduodenoscopy revealed an elevated lesion with a central ulcer in the upper body of the stomach, and biopsy specimens confirmed the pathological diagnosis of NET G3. Abdominal contrast-enhanced computed tomography (CT) showed a 25-cm, well-defined mass lesion showing heterogeneous enhancement in the liver. A clinical diagnosis of NET G3 with multiple liver metastases was given, after which everolimus was administered in combination with a somatostatin analogue. However, the patient developed sudden-onset epigastric abdominal pain and general fatigue 2 months later, and emergency abdominal contrast-enhanced CT confirmed the presence of intra-abdominal hemorrhage. Following blood transfusion, the patient's symptoms and general condition improved. Although the patient was treated with streptozocin, abdominal CT indicated progression of the liver metastases. Unfortunately, despite receiving best supportive care, the patient died 8 months after the initial of the treatment. To the best of our knowledge, this is the first case of a patient who developed spontaneous hemoperitoneum during drug treatment for a NET G3 to be reported in the English literature. It is essential that additional data be obtained to determine the optimal treatment for this disease.

Evolution of life cycle dimorphism: An example of sacoglossan sea slugs.

Many sea slugs of Sacoglossa (Mollusca: Heterobranchia) are sometimes called "solar-powered sea slugs" because they keep chloroplasts obtained from their food algae and receive photosynthetic products (termed kleptoplasty). Some species show life cycle dimorphism, in which a single species has some individuals with a complex life cycle (the mother produces planktotrophic larvae, which later settle in the adult habitat) and others with a simple life cycle (mothers produce benthic offspring by direct development or short-term nonfeeding larvae in which feeding planktonic stages are skipped). Life cycle dimorphism is not common among marine species. In this paper, we ask whether some aspects of the ecology of solar-powered sea slugs have promoted the evolution of life cycle dimorphism in them. We study the population dynamics of the two life-cycle types that differ in summer (one with planktonic life and the other with benthic life), but both have benthic life in other seasons. We obtain the conditions in which two types with different life cycles coexist stably or a single type generating offspring with different life cycles evolves. We conclude that the stable coexistence of two life cycles can evolve if benthic individuals in summer experience strongly density-dependent processes or if the between-year fluctuation of biomass growth in summer is very large. We discuss whether these results match the life cycles of solar-powered sea slugs with life cycle dimorphism.

Real-time bowel sound analysis using newly developed device in patients undergoing gastric surgery for gastric tumor.

BACKGROUND AND AIM: Objective measurements are not available for determining bowel sounds. The present study sought to evaluate the efficacy of a novel bowel sound monitoring system for perioperative use in patients undergoing gastric surgery. METHODS: The study enrolled 14 patients who underwent surgery for gastric cancer at Kochi Medical School from 2017 to 2018. Preoperative and postoperative bowel sounds were recorded using a newly developed real-time analysis system in the operating theater and recovery room. Clinical information and bowel sound count data were obtained to compare preoperative and postoperative measures. RESULTS: The median preoperative and postoperative bowel sound counts across all patients were 1.4 and 2.5 counts per minute (cpm), respectively. In patients who underwent laparoscopic gastrectomy, the postoperative bowel sound count was significantly higher than that recorded preoperatively (2.3 vs. 1.6 cpm, P = 0.005). The findings also revealed a significant negative correlation between postoperative bowel sound count and operation time (r = -0.714, P = 0.003). CONCLUSIONS: The real-time bowel sound analysis system tested herein presents a promising diagnostic tool to quantitatively evaluate bowel movements associated with surgery. Our results suggested a need for shorter operation times for gastric procedures with respect to peristalsis recovery and supported the use of minimally invasive surgery.

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.

Evolutionary game in an androdioecious population: Coupling of outcrossing and male production.

Androdioecy, the coexistence of hermaphrodites and males, is very rare in vertebrates but occurs in mangrove killifish living in ephemeral or unstable habitats. Hermaphrodites reproduce both by outcrossing with males and by selfing. Outbreeding is advantageous because of inbreeding depression, but it requires encounters with males. The advantages of a propensity for outcrossing among hermaphrodites and the production of males affect each other very strongly. To study the evolutionary coupling of these two aspects, we here analyze a simple evolutionary game for a population composed of three phenotypes: outcrossing-oriented hermaphrodites, selfing-oriented hermaphrodites, and males. Outcrossing-oriented hermaphrodites first attempt to search for males and perform outcrossing if they encounter males. If they fail to encounter males, they reproduce via selfing. Selfing-oriented hermaphrodites simply reproduce by selfing. The replicator dynamics may show bistability, in which both the androdioecious population (with outcrossing-oriented hermaphrodites and males) and the pure hermaphroditic population are locally stable. The model shows the fraction of males is either zero or relatively high (more than 25%), which is not consistent with the observed low fraction of males (less than 5%). To explain this discrepancy, we studied several models including immigration and enforced copulation. We concluded that the observed pattern can be most likely explained by a population dominated by selfing-oriented hermaphrodites receiving immigration of males.

Optimal control of root nodulation - Prediction of life history theory of a mutualistic system.

Legumes produce root nodules containing symbiotic rhizobial bacteria that convert atmospheric molecular nitrogen into ammonia or related nitrogenous compounds. The host plant supplies photosynthetic products to root nodules forming a mutualistic system. Legumes have physiological mechanisms for regulating nodule production with chemical signals produced in leaves, called the autoregulation of nodulation. In this paper, we discuss the optimal number of root nodules that maximizes the performance of the host plant. Here, we study two models. In the stationary plant model, the acquired photosynthetic products minus cost and loss are used for reproduction. In the growing plant model, the excess material is invested to produce leaves, roots, and root nodules, resulting in the exponential growth of the whole plant. The analysis shows that having root nodules is beneficial to the plant for a high leaf nitrogen content, faster plant growth rate, a short leaf longevity, a low root/shoot ratio, and low soil nutrient concentration. We discuss the long-distance control of nodulation-autoregulation and dependence on the environmental conditions of terrestrial plants considering these results.

Gastric Eosinophilic Granuloma Related to Anisakiasis Resected by Laparoscopic and Endoscopic Cooperative Surgery.

Background: Anisakiasis-related gastric eosinophilic granuloma is rare. Case Report: Herein, we report a patient with anisakiasis-related gastric eosinophilic granuloma who was treated with laparoscopic and endoscopic cooperative surgery (LECS). A 59-year-old woman was presented to our hospital for further examination of a gastric lesion that was initially diagnosed by a local medical doctor. Esophagogastroduodenoscopy showed a submucosal tumor-like lesion in the lower body of the stomach. Endoscopic ultrasonography showed a heterogeneous hypoechoic submucosal mass lesion in the submucosal layer measuring 10 mm, without evidence of deep involvement. Under a clinical diagnosis of gastrointestinal stromal tumor, the patient underwent LECS. Gross appearance of the resected specimen revealed a 1.5×1.0 cm submucosal tumor-like lesion. Microscopic examination revealed necrosed insects consistent with the characteristics of gastric anisakiasis, around which prominent eosinophilic infiltration and granulomas were observed. This prompted a diagnosis of gastric eosinophilic granuloma related to anisakiasis. Conclusion: To the best of our knowledge, this is the second case of gastric eosinophilic granuloma related to anisakiasis resected by LECS in the English medical literature. LECS might be a useful procedure for minimally invasive therapeutic diagnosis.

Enhanced risk of cancer in companion animals as a response to the longevity.

Cancer is caused by the lifetime accumulation of multiple somatic deformations of the genome and epigenome. At a very low rate, mistakes occur during genomic replication (e.g., mutations or modified epigenetic marks). Long-lived species, such as elephants, are suggested to have evolved mechanisms to slow down the cancer progression. Recently, the life span of companion dogs has increased considerably than before, owing to the improvement of their environment, which has led to an increase in the fraction of companion dogs developing cancer. These findings suggest that short-term responses of cancer risk to longevity differ from long-term responses. In this study, to clarify the situation, we used a simple multi-step model for cancer. The rates of events leading to malignant cancer are assumed to be proportional to those of genomic replication error. Perfect removal of replication error requires a large cost, resulting in the evolution of a positive rate of genomic replication error. The analysis of the model revealed: that, when the environment suddenly becomes benign, the relative importance of cancer enhances, although the age-dependent cancer risk remains unchanged. However, in the long run, the genomic error rate evolves to become smaller and mitigates the cancer risk.

Bovine mastitis and optimal disease management: Dynamic programming analysis.

Wise decision-making for coping with infectious diseases is a key to the success of farming, agriculture, as well as public health. Mastitis of dairy cows causes large economic burden to dairy farmers. Here, we study the optimal operation for a dairy farmer to manage cows infected by mastitis. In the simple model, we considered cows with different number of breasts (quarters) infected by mastitis. In the detailed model, we considered additional complexities: a cow produces milk only after the first birth of a calf, old cows are culled, milking is not practiced for 10 weeks prior to expected calf-birth, and a newborn calf provides an economic benefit. By fitting the parameters to the Japanese dairy farming situation, the dynamic programming analysis reveals whether an infected cow should receive medical treatment depends on the number of breasts infected, age, and season. Cows should be culled if many breasts are infected, they are old, and it is not close to the next calf-birth. The optimal management policy depends critically on milk price, maintenance cost, and recovery rate from mastitis infection, but not on infection rate.

Evaluation of Systemic Inflammatory Response and Nutritional Biomarkers as Predictive Factors in Patients with Recurrent Gastric Cancer.

BACKGROUND: The present study sought to evaluate host-related factors as predictors in patients receiving chemotherapy for recurrent advanced gastric cancer. METHODS: Sixty-three patients were enrolled in the study and received chemotherapy for recurrent gastric cancer at the Kochi Medical School from 2008 to 2015. Clinicopathological information and systemic inflammatory response data were obtained retrospectively to investigate associations between baseline cancer-related prognostic variables and survival outcomes. RESULTS: The median survival time was significantly higher for patients with a Glasgow prognostic score (GPS) of 0 compared to a GPS of 1 or 2 (18.2 vs. 7.1 months; p = 0.006), and for patients in the normal range for carbohydrate antigen-125 (CA125) compared to higher levels (17.9 vs. 4.1 months; p = 0.003). There was no significant influence on overall survival by age, gender, disease status, metastatic site, time to recurrence, carcinoembryonic antigen level, CA19-9 level, prognostic nutrition index, or neutrophil to lymphocyte ratio according to the results of the univariate log-rank tests. Multivariate survival analysis identified a GPS of 1 or 2 (hazard ratio, 3.520; 95% confidence interval, 1.343-9.227; p = 0.010) and a high CA125 level (hazard ratio, 3.135; 95% confidence interval, 1.276-7.697; p = 0.013) as significant independent predictors associated with a poorer prognosis in the studied group of cancer patients. CONCLUSIONS: A GPS of 1 or 2 and a high level of CA125 are independent predictors of a poorer prognosis in patients receiving chemotherapy for recurrent gastric cancer.

Task allocation in a cooperative society: specialized castes or age-dependent switching among ant workers.

Some ant species have multiple worker castes that differ in body size; workers in one caste remain in the colony and those in the other forage outside the colony (caste polyethism). In other species, all workers engage in both tasks, but the younger workers remain in the colony and the older workers forage (age polyethism). Here, we ask which of these two is the most efficient for colony level performance when foragers suffer a higher daily mortality than workers in the colony and when the optimal worker size differs between two tasks. We studied two models: in the stationary colony model, the colony size and composition remain constant, and the amount of excess resources that can be used for producing reproductive individuals is maximized; in the growing colony model, all of the resources obtained are used for producing new workers, and the rate of the colony growth is maximized. In both models, we observed similar results: caste polyethism is more advantageous than age polyethism if the difference in mortality between the two tasks is small and the difference in the optimal size is large. In the opposite situation, the age polyethism is more advantageous.

Why is bidirectional sex change rare?

Various species of fish living in coral reef communities show sequential hermaphroditism, or sex change. In a typical case, an individual first matures as a female, and later, when it becomes dominant in the mating group, it becomes a male (i.e., protogynous sex change). Many species show only unidirectional changes but some of coral reef fishes exhibit bidirectional sex changes, in which even a dominant male may revert to female when a socially more dominant competitor arrives. However, bidirectional sex change has rarely been observed in natural conditions, even among those species exhibiting it under experimental conditions. Here we explain the rarity of bidirectional sex change by studying dynamics of hormones controlling sex expression. We consider social status factor, SF, which is elevated when the individual becomes more dominant in the mating group. When the SF level is high, the dynamics would culminate with low estradiol expression and high testosterone expression, suggesting a male phenotype. In contrast, when SF level is low, the system converges to an equilibrium with high estradiol expression and low testosterone expression, suggesting a female phenotype. There is a parameter region in which the dynamics exhibit bistability. The model demonstrates hysteresis: as SF increases smoothly, the system undergoes a sudden transition in the levels of sex hormones. The model can explain why species show unidirectional sex change, in that an individual's switch to a new sex is irreversible, even if the individual's social situation returns to the original subdominant status.