Multiple sarcomatoid carcinomas in the small intestine with perforation: A case report and literature review.

RATIONALE: Sarcomatoid carcinoma of the small intestine is an exceedingly rare and aggressive malignancy, often diagnosed at advanced stages with a poor prognosis. This study documents a detailed case of sarcomatoid carcinoma of the small intestine, highlighting the diagnostic challenges and treatment approaches, underscored by a comprehensive review of related literature. Given the rarity of this condition, our report aims to enrich the existing diagnostic and treatment frameworks for this malignancy, emphasizing the necessity for early detection and intervention strategies. By presenting this case in conjunction with a literature review, we seek to shed light on the elusive nature of sarcomatoid carcinoma in the small intestine and propose avenues for improving patient outcomes. PATIENT CONCERNS: Case presentation A 61-year-old male patient initially presented with recurrent abdominal pain and gastrointestinal symptoms. Initial abdominal computed tomography (CT) scans and gastrointestinal endoscopy revealed only inflammatory and hyperplastic changes in the duodenum and jejunum, with a diagnosis of intestinal obstruction. Two years later, due to gastrointestinal perforation, the patient was hospitalized again. DIAGNOSES: CT scans and other examinations revealed small intestinal lesions. Four small intestinal lesions were surgically removed, and pathology and immunohistochemistry confirmed sarcomatoid carcinoma of the small intestine. A short time later, enhanced CT scans revealed metastatic lesions in the hepatic portal and adrenal glands. INTERVENTIONS: After surgery, the gastrointestinal function gradually recovered, and the patient was discharged from the hospital on a semiliquid diet. No further treatment such as radiotherapy or chemotherapy was administered postoperatively. OUTCOMES: Five months after the surgery, the patient died due to brain metastasis. LESSONS: The study outcomes reveal the aggressive nature of sarcomatoid carcinoma of the small intestine, characterized by rapid progression and poor prognosis despite surgical interventions. The patient condition rapidly deteriorated, leading to metastasis and death within 5 months postsurgery. These findings underscore the critical need for early detection and possibly innovative treatment approaches to improve survival rates. This case also highlights the potential for gastrointestinal sarcomatoid carcinoma to metastasize to distant organs, including the brain, suggesting a propensity for hematogenous spread.

Time-to-surgery paradigms: wait time and surgical outcomes in critically Ill patients who underwent emergency surgery for gastrointestinal perforation.

BACKGROUND: Waiting time for emergency abdominal surgery have been known to be linked to mortality. However, there is no clear consensus on the appropriated timing of surgery for gastrointestinal perforation. We investigated association between wait time and surgical outcomes in emergency abdominal surgery. METHODS: This single-center retrospective cohort study evaluated adult patients who underwent emergency surgery for gastrointestinal perforations between January 2003 and September 2021. Risk-adjusted restricted cubic splines modeled the probability of each mortality according to wait time. The inflection point when mortality began to increase was used to define early and late surgery. Outcomes among propensity-score matched early and late surgical patients were compared using percent absolute risk differences (RDs, with 95% CIs). RESULTS: Mortality rates began to rise after 16 h of waiting. However, early and late surgery groups showed no significant differences in 30-day mortality (11.4% vs. 5.7%), ICU stay duration (4.3 ± 7.5 vs. 4.3 ± 5.2 days), or total hospital stay (17.4 ± 17.0 vs. 24.7 ± 23.4 days). Notably, patients waiting over 16 h had a significantly higher ICU readmission rate (8.6% vs. 31.4%). The APACHE II score was a significant predictor of 30-day mortality. CONCLUSIONS: Although we were unable to reveal significant differences in mortality in the subgroup analysis, we were able to find an inflection point of 16 h through the RCS curve technique. TRIAL REGISTRATION: Formal consent was waived due to the retrospective nature of the study, and ethical approval was obtained from the institutional research committee of our institution (B-2110-714-107) on 6 October 2021.

[A case of small intestinal endometriosis with bowel obstruction and perforation].

A 47-year-old woman was referred to our hospital with recurring lower abdominal pain persisting for more than 2 weeks. Imaging modalities showed small bowel obstruction caused by a mass lesion in the terminal ileum. Despite undergoing fasting, rehydration, and decompression through an ileus tube, her symptoms persisted. Furthermore, the condition deteriorated on day 4, with the onset of her menstrual period. An emergency surgery was conducted on the 7th day after hospitalization. Surgical observations indicated severe stenosis around the ileocecal valve and ileal perforation approximately 40cm from the oral stricture. As a result, ileocecal resection was performed. Pathological examination revealed endometrial tissue infiltration through the mucosal lamina propria to the ileal subserosa. Thus, the patient was identified with intestinal endometriosis of the ileocecum. Endometriosis of the small bowel is an uncommon condition that eventually causes intractable bowel obstruction. Although preoperative diagnosis is considered challenging, intestinal endometriosis should be included in the differential diagnosis in cases of bowel obstruction in women of childbearing age.

Evaluation of laparoscopic peritoneal lavage for perforated diverticulitis: a national registry-based study.

BACKGROUND: Laparoscopic lavage (LPL) has been suggested for treatment of non-feculent perforated diverticulitis. In this observational study, the surgical treatment of diverticular disease in Sweden outside prospective trials was investigated. METHODS: This population-based study used the National Patient Register to identify all patients in Sweden with emergency admissions for diverticular disease, as defined by ICD codes from July 2014 to December 2020. Demographics, surgical procedures and outcomes were assessed. In addition, register data since 1997 were retrieved to assess co-morbidities, previous abdominal surgeries, and previous admissions for diverticular disease. RESULTS: Among 47 294 patients with emergency hospital admission, 2035 underwent LPL (427 patients) or sigmoid resection (SR, 1608 patients) for diverticular disease. The mean follow-up was 30.8 months. Patients selected for LPL were younger, healthier and with less previous abdominal surgery for diverticular disease than those in the SR group (P < 0.01). LPL was associated with shorter postoperative hospital stay (mean 9.4 versus 14.9 days, P < 0.001) and lower 30-day mortality (3.5% versus 8.7%, P < 0.001). Diverticular disease-associated subsequent surgery was more common in the SR group than the LPL group except during the first year (P < 0.001). LPL had a lower mortality rate during the study period (stratified HR 0.70, 95% c.i. 0.53-0.92, P = 0.023). CONCLUSION: Laparoscopic lavage constitutes a safe alternative to sigmoid resection for selected patients judged clinically to require surgery.

Diverticulitis is inflammation in pouches of the large bowel. Rarely, diverticulitis can lead to a bowel perforation causing peritonitis. Traditionally, it was treated by resection of the inflamed bowel with a stoma. A milder treatment has been proposed in which the abdomen is rinsed with saline laparoscopically and drained (laparoscopic lavage). This study aimed to examine the outcomes of laparoscopic lavage in Sweden. Our findings support the use of this method in younger and healthier patients with a history of no or only minor previous abdominal surgery.

Intestinal perforation due to colorectal cancer during pregnancy: case report and literature review.

Colorectal cancer (CRC) in pregnancy is sporadic. We reported a case of a woman at 23 + 4 weeks of gestation who presented with abdominal pain. The patient underwent an ultrasound and MRI, during which a colonic mass was noted. Considering a probable incomplete intestinal obstruction, a colonoscopy, biopsy, and colonic stenting were performed by a multidisciplinary team. However, sudden hyperthermia and CT demonstrated intestinal perforation, and an emergency caesarean section and colostomy were conducted. The histological analysis confirmed moderately high-grade adenocarcinoma.

Changes of PK/PD of Meropenem in patients with abdominal septic shock and exploration of clinical rational administration plan: a prospective exploratory study.

This study aimed to explore the changes of pharmacokinetic parameters after meropenem in patients with abdominal septic shock after gastrointestinal perforation, and to simulate the probability of different dosing regimens achieving different pharmacodynamic goals. The study included 12 patients, and utilized high performance liquid chromatography-tandem mass spectrometry to monitor the plasma concentration of meropenem. The probability of target attainment (PTA) for different minimum inhibitory concentration (MIC) values and %fT > 4MIC was compared among simulated dosing regimens. The results showed that in 96 blood samples from 12 patients, the clearance (CL) of meropenem in the normal and abnormal creatinine clearance subgroups were 7.7 ± 1.8 and 4.4 ± 1.1 L/h, respectively, and the apparent volume of distribution (Vd) was 22.6 ± 5.1 and 17.2 ± 5.8 L, respectively. 2. Regardless of the subgroup, 0.5 g/q6h infusion over 6 h regimen achieved a PTA > 90% when MIC ≤ 0.5 mg/L. 1.0 g/q6h infusion regimen compared with other regimen, in most cases, the probability of making PTA > 90% is higher. For patients at low MIC, 0.5 g/q6h infusion over 6 h may be preferable. For patients at high MIC, a dose regimen of 1.0 g/q6 h infusion over 6 h may be preferable. Further research is needed to confirm this exploratory result.

Management of perforations during endoscopic resection.

Despite the evolution in tools and techniques, perforation is still one of the most pernicious adverse events of therapeutic endoscopy with potentially huge consequences. As advanced endoscopic resection techniques are worldwide spreading, endoscopists must be ready to manage intraprocedural perforations. In fact, immediate endoscopic closure through a prompt diagnosis represents the first-line option, saving patients from surgery, long hospitalizations and worse outcomes. Traditional and novel endoscopic closure modalities, including clips, suturing devices, stents and vacuum therapy, are increasingly expanding the therapeutic armamentarium for closing these defects. Nevertheless, available literature on this topic is currently limited. In this review our goal is to give an overview on the management of perforations occurring during endoscopic resections, with particular attention to characteristics, advantages, disadvantages and new horizons of endoscopic closure tools.

Surgical Emergencies in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) patients are at risk for undergoing emergency surgery for fulminant disease, toxic megacolon, bowel perforation, intestinal obstruction, or uncontrolled gastrointestinal hemorrhage. Unfortunately, medical advancements have failed to significantly decrease rates of emergency surgery for IBD. It is therefore important for all acute care and colorectal surgeons to understand the unique considerations owed to this often-challenging patient population.

Long term survival outcomes of surgery combined with hyperthermic intraperitoneal chemotherapy for perforated low-grade appendiceal mucinous neoplasms: A multicenter retrospective study.

BACKGROUND: Low-grade appendiceal mucinous neoplasms (LAMN) are very rare, accounting for approximately 0.2%-0.5% of gastrointestinal tumors. We conducted a multicenter retrospective study to explore the impact of different surgical procedures combined with HIPEC on the short-term outcomes and long-term survival of patients. METHODS: We retrospectively analyzed the clinicopathological data of 91 LAMN perforation patients from 9 teaching hospitals over a 10-year period, and divided them into HIPEC group and non-HIPEC group based on whether or not underwent HIPEC. RESULTS: Of the 91 patients with LAMN, 52 were in the HIPEC group and 39 in the non-HIPEC group. The Kaplan-Meier method predicted that 52 patients in the HIPEC group had 5- and 10-year overall survival rates of 82.7% and 76.9%, respectively, compared with predicted survival rates of 51.3% and 46.2% for the 39 patients in the non-HIPEC group, with a statistically significant difference between the two groups (χ2 = 10.622, p = 0.001; χ2 = 10.995, p = 0.001). Compared to the 5-year and 10-year relapse-free survival rates of 75.0% and 65.4% in the HIPEC group, respectively, the 5-year and 10-year relapse-free survival rates of 48.7% and 46.2% in the non-HIPEC group were significant different between the two outcomes (χ2 = 8.063, p = 0.005; χ2 = 6.775, p = 0.009). The incidence of postoperative electrolyte disturbances and hypoalbuminemia was significantly higher in the HIPEC group than in the non-HIPEC group (p = 0.023; p = 0.044). CONCLUSIONS: This study shows that surgery combined with HIPEC can significantly improve 5-year and 10-year overall survival rates and relapse-free survival rates of LAMN perforation patients, without affecting their short-term clinical outcomes.

Perforation of barium sulfate enterography in an infant: A case report.

RATIONALE: Barium peritonitis is an inflammatory response that occurs when barium accidentally enters the abdominal cavity during a barium test. In extreme circumstances, it has the potential to harm various organs and even result in death. PATIENT CONCERNS: A 3-month-old infant was diagnosed with multiple organ failure after severe barium peritonitis. DIAGNOSIS: Multiple organ dysfunction is associated with barium peritonitis. INTERVENTIONS: The infant underwent surgical intervention and received ventilator support, anti-infection therapy, myocardial nutrition, liver and kidney protection, rehydration, circulation stabilization, and other symptomatic supportive care. OUTCOMES: The patient experienced clinical death after treatment and resuscitation was unsuccessful. LESSONS: Barium enema perforation complications are uncommon, but can lead to fatal injuries with a high mortality rate. This case highlights the importance of raising awareness among clinicians about the risks of gastroenterography in infants and children and actively preventing and avoiding similar serious complications. The mortality rate can be reduced by timely multidisciplinary consultation and joint management once a perforation occurs.

Bowel perforation with generalised peritonitis secondary to recurrent primary fallopian tube carcinoma after 17 years.

We describe a case of bowel perforation secondary to a recurrence of primary fallopian tube carcinoma treated more than a decade ago. A woman in her 70s presented to a rural centre with an acute abdomen. An abdominal CT showed a perforated ileum secondary to a pelvic mass. Emergency laparotomy identified the pelvic mass that was adherent to the side wall and invading the ileum at the site of perforation. Its adherence to the external iliac vessels posed a challenge to achieve en-bloc resection; therefore, a defunctioning loop ileostomy was created. Final histopathology and immunopathology were consistent with the recurrence of her primary fallopian tube carcinoma. The patient was further discussed in a multidisciplinary team meeting at a tertiary referral hospital. This case highlighted the importance of having a high index of suspicion for cancer recurrence, the utility of rapid source control laparotomy and multidisciplinary team patient management.

Pneumoperitoneum, pneumoretroperitoneum and pneumomediastinum: rare complications of perforation peritonitis: a case report.

BACKGROUND: Gas extravasation complications arising from perforated diverticulitis are common but manifestations such as pneumoperitoneum, pneumoretroperitoneum, and pneumomediastinum happening at the same time are exceedingly rare. This case report explores the unique presentation of these 3 complications occurring simultaneously, their diagnosis and their management, emphasizing the importance of interdisciplinary collaboration for accurate diagnosis and effective management. CASE PRESENTATION: A 74-year-old North African female, with a medical history including hypertension, dyslipidemia, type 2 diabetes, goiter, prior cholecystectomy, and bilateral total knee replacement, presented with sudden-onset pelvic pain, chronic constipation, and rectal bleeding. Clinical examination revealed hemodynamic instability, hypoxemia, and diffuse tenderness. After appropriate fluid resuscitation with norepinephrine and saline serum, the patient was stable enough to undergo computed tomography scan. Emergency computed tomography scan confirmed perforated diverticulitis at the rectosigmoid junction, accompanied by the unprecedented presence of pneumoperitoneum, pneumoretroperitoneum, and pneumomediastinum. The patient underwent prompt surgical intervention with colo-rectal resection and a Hartmann colostomy. The postoperative course was favorable, leading to discharge one week after admission. CONCLUSIONS: This case report highlights the clinical novelty of gas extravasation complications in perforated diverticulitis. The unique triad of pneumoperitoneum, pneumoretroperitoneum, and pneumomediastinum in a 74-year-old female underscores the diagnostic challenges and the importance of advanced imaging techniques. The successful collaboration between radiologists and surgeons facilitated a timely and accurate diagnosis, enabling a minimally invasive surgical approach. This case contributes to the understanding of atypical presentations of diverticulitis and emphasizes the significance of interdisciplinary teamwork in managing such rare manifestations.

[Necrosis and intestinal perforation associated with feeding by jejunostomy]. / Necrosis y perforación intestinal asociada a alimentación por yeyunostomía.

Enteral nutrition through jejunostomy is a common practice in any general surgery service; it carries a low risk of complications and morbidity and mortality. We present the case of a patient with an immediate history of subtotal gastrectomy that began nutrition through jejunostomy and complicated with intestinal necrosis due to non-occlusive ischemia in the short period. The purpose of this work is to report on this complication, its pathophysiology and risk factors to take it into account and be able to take appropriate therapeutic action early.

La nutrición enteral por yeyunostomía es una práctica frecuente en cualquier servicio de cirugía general, esta conlleva bajo riesgo de complicaciones y morbimortalidad. Presentamos el caso de una paciente con antecedente inmediato de gastrectomía subtotal que inició nutrición por yeyunostomía y complicó con necrosis intestinal por isquemia no oclusiva en el corto lapso. La finalidad de este trabajo es informar sobre esta complicación, su fisiopatología y factores de riesgo para tenerla en cuenta y poder tomar precozmente una conducta terapéutica adecuada.

Factores asociados al desenlace en niños con mal rotación intestinal manejados en el Hospital Infantil de San Vicente Fundación, Medellín, Colombia / Factors associated with outcome in children with intestinal malrotation managed at the Hospital Infantil of San Vicente Fundación, Medellín, Colombia

Introducción. El intestino primitivo rota durante la vida embrionaria. Cuando ocurre de forma inadecuada aparece la malrotación intestinal que puede llevar a la obstrucción o al vólvulo del intestino medio. La incidencia disminuye con el aumento de la edad. La malrotación intestinal es una de las principales causas de complicaciones del tracto gastrointestinal en la edad pediátrica. Métodos. Estudio retrospectivo, observacional, transversal y analítico, de la experiencia durante 10 años en pacientes menores de 15 años con diagnóstico de malrotación intestinal, tratados en el Hospital Infantil de San Vicente Fundación, en Medellín, Colombia. Se buscó la asociación entre variables demográficas, clínicas e imagenológicas con los desenlaces. Resultados. Se obtuvieron 58 pacientes con malrotación intestinal, 65 % menores de 1 año. En 29,3 % de los pacientes se hizo el diagnóstico con la presentación clínica; los síntomas predominantes fueron distensión abdominal y emesis. En el 24,1 % se confirmó el diagnóstico con imágenes. Las variables con una diferencia estadísticamente significativa a favor de encontrar una malrotación complicada fueron choque séptico (OR=11,7), síndrome de respuesta inflamatoria sistémica (OR=8,4) y deshidratación (OR=5,18). Conclusiones. La malrotación intestinal tiene complicaciones como perforación, peritonitis, vólvulo e intestino corto. El vólvulo se acompaña de shock y sepsis, con mortalidad hasta del 50 %. Las imágenes diagnósticas son una ayuda, pero no se puede basar la conducta médica en estas porque ninguna imagen garantiza el diagnóstico definitivo. Los signos de alarma son poco específicos. En menores de un año con emesis, distensión y dolor abdominal se debe sospechar malrotación intestinal.

Introduction. The primitive intestine rotates during embryonic life. When it occurs inappropriately, intestinal malrotation appears, which can lead to obstruction or midgut volvulus. The incidence decreases when age increases. Intestinal malrotation is one of the main causes of complications of the gastrointestinal tract in pediatric age. Method. Retrospective, observational, cross-sectional and analytical study of the experience over 10 years in patients under 15 years of age with a diagnosis of intestinal malrotation, treated at Hospital Infantil of San Vicente Fundación, in Medellín, Colombia. The association between demographic, clinical and imaging variables with the outcomes was sought. Results. There were 58 patients with intestinal malrotation, 65% under one year of age. In 29.3% of patients, intestinal malrotation was diagnosed clinically. The predominant symptoms were abdominal distension and emesis. In 24.1% the diagnosis was confirmed with imaging. The variables with a statistically significant difference in favor of finding a complicated malrotation were septic shock (OR=11.7), systemic inflammatory response syndrome (OR-8.4), and dehydration (OR=5.18). Conclusions. Malrotation has complications such as perforation, peritonitis, volvulus, and short bowel. Volvulus is accompanied by shock and sepsis, with mortality of up to 50%. Diagnostic images are helpful, but medical conduct cannot be based on them because no image guarantees a definitive diagnosis. The warning signs are not very specific. In children under one year of age with emesis, distension and abdominal pain, intestinal malrotation should be suspected.

Fascitis necrosante como causa de muerte en trauma de recto. Reporte de caso / Necrotizing fasciitis as a cause of death in rectal trauma. Case report

Introducción. La perforación del recto por trauma cerrado es poco frecuente y se asocia a fracturas pélvicas. En pacientes con perforaciones de recto no traumáticas se ha reportado fascitis necrosante en miembros inferiores, en la mayoría de los casos asociada a alta mortalidad. Caso clínico. Hombre de 36 años con trauma cerrado abdomino-pélvico y perforación de recto inferior, quien recibió manejo quirúrgico mediante derivación intestinal y fijación pélvica. Evolucionó con hematoma escrotal sobreinfectado, inestabilidad hemodinámica, signos de fascitis necrosante y choque séptico 4 días posterior a su ingreso. Resultados. Se tomó muestra para cultivo del hematoma escrotal que reportó E. coli. La patología del desbridamiento escrotal informó necrosis de coagulación en toda la muestra. Conclusión. El tacto rectal debe realizarse siempre ante la presencia de enfisema subcutáneo al examen físico o en la tomografía, para un diagnóstico temprano y manejo quirúrgico multidisciplinario oportuno, según el caso. La presencia de enfisema subcutáneo debe aumentar la sospecha de perforación de recto. Hay pocos reportes de fascitis secundaria a perforación de recto por trauma cerrado, por lo que no se conoce con precisión la mortalidad asociada.

Introduction. Rectal perforation due to blunt trauma is rare and associated with pelvic fractures. Signs of necrotizing fasciitis in lower limbs have been reported in non-traumatic rectal perforations, in most cases associated with high mortality. Case report. A 36-year-old man presents blunt abdomino-pelvic trauma and perforation of the lower rectum. Surgical management by intestinal diversion and pelvic fixation is performed. 4 days after admission, evolves with over-infected scrotal hematoma, hemodynamic instability, signs of necrotizing fasciitis and septic shock. Results. A sample for culture was taken from a scrotal hematoma that reported E. coli. Pathology of scrotal debridement reported coagulation necrosis in the entire specimen. Discussion. Digital rectal examination should always be performed in the presence of subcutaneous emphysema on physical examination or CT scan for early and multidisciplinary diagnosis and surgical management as appropriate. Conclusion. The presence of subcutaneous emphysema should raise the suspicion of rectal perforation. There are few reports of rectal perforation due to blunt trauma and fasciitis, so the associated mortality is not precisely known.

A first-in-human clinical study of laparoscopic autologous myoblast sheet transplantation to prevent delayed perforation after duodenal endoscopic mucosal dissection.

BACKGROUND: The detection rate of superficial non-ampullary duodenal epithelial tumors (SNADETs) has recently been increasing. Large tumors may contain malignant lesions and early therapeutic intervention is recommended. Endoscopic mucosal dissection (ESD) is considered a feasible treatment modality, however, the anatomical and physiological characteristics of the duodenum create a risk of postoperative perforation after ESD. METHODS: To explore whether myoblast sheet transplantation could prevent delayed perforation after ESD, a first-in-human (FIH) clinical trial of laparoscopic autologous myoblast sheet transplantation after duodenal ESD was launched. Autologous myoblast sheets fabricated from muscle tissue obtained seven weeks before ESD were transplanted laparoscopically onto the serous side of the ESD. The primary endpoints were the onset of peritonitis due to delayed perforation within three days after surgery and all adverse events during the follow-up period. RESULTS: Three patients with SNADETs ≥ 20 mm in size underwent transplantation of a myoblast sheet onto the serous side of the duodenum after ESD. In case 1, The patient's postoperative course was uneventful. Endoscopy and abdominal computed tomography revealed no signs of delayed perforation. Despite incomplete mucosal closure in case 2, and multiple micro perforations during ESD in case 3, cell sheet transplantation could prevent the postoperative massive perforation after ESD, and endoscopy on day 49 after transplantation revealed no stenosis. CONCLUSIONS: This clinical trial showed the safety, efficacy, and procedural operability of this novel regenerative medicine approach involving transplanting an autologous myoblast sheet laparoscopically onto the serosa after ESD in cases with a high risk of delayed perforation. This result indicates the potential application of cell sheet medicine in treating various abdominal organs and conditions with minimal invasiveness in the future. TRIAL REGISTRATION: jRCT, jRCT2073210094. Registered November 8 2021, https://jrct.niph.go.jp/latest-detail/jRCT2073210094 .

Colorectal Oncologic Emergencies: Recognition, Management, and Outcomes.

Colorectal cancer is the third most frequent type of malignancy in the United States, and the age at diagnosis is decreasing. Although the goal of screening is focused on prevention and early detection, a subset of patients inevitably presents as oncologic emergencies. Approximately 15% of patients with colorectal cancer will present as surgical emergencies, with the majority being due to either colonic perforation or obstruction. Patients presenting with colorectal emergencies are a challenging cohort, as they often present at an advanced stage with an increase in T stage, lymphovascular invasion, and metachronous liver disease.