Evaluation of histopathological heterogeneity of colorectal cancer liver metastasis sites after preoperative chemotherapy.

Patients with liver metastases from colorectal cancer (CRLMs) frequently receive chemotherapy prior to liver resection. Histopathological assessment of the resected specimen can evaluate the response to chemotherapy. The present study analyzed the association between histopathological changes in the primary site and liver metastases. The present study comprised 45 patients with resectable CRLMs at the Surgical Oncology Department of Gifu University School of Medicine (Gifu, Japan) between January 2006 and August 2015. The study included 24 men and 21 women. The primary colonic tumor was located in the right side in 13 (28.9%) patients and the left side in 32 (71.9%) patients. The present study evaluated patients with metastatic colorectal cancer (31/45) after excluding those in whom histopathological heterogeneity between the primary and liver metastasis changed to grade 3 after chemotherapy. The group that underwent hepatectomy after chemotherapy (n=25) was compared with the group that underwent hepatectomy alone (n=6). In 16 (53.3%) out of 25 patients, histopathological heterogeneity of the liver metastasis was lost (P=0.04). In conclusion, chemotherapy appeared to change histopathological heterogeneity. The present study suggested that the histopathological change of intratumoral heterogeneity is reflected by the response to chemotherapy.

Atraumatic splenic rupture and infection-related glomerulonephritis in a patient with infected aortic aneurysm: A case report.

INTRODUCTION: Atraumatic splenic rupture is very rare and the case is often difficult to determine. We report a case of atraumatic splenic rupture in a patient with an infected aortic aneurysm. CASE PRESENTATION: A 40-year-old man under evaluation and treatment for renal dysfunction presented with the sudden onset of epigastric pain. The patient had a previous history of aortic arch replacement for Stanford type B aortic dissection. Contrast-enhanced computed tomography revealed intraabdominal hemorrhaging around the spleen and intrasplenic extravasation of contrast medium, and atraumatic splenic rupture was diagnosed. The patient slipped into hemorrhagic shock, and emergency splenectomy was scheduled. The histopathological diagnosis was splenic rupture with splenic infarction. The patient became febrile on postoperative day 10. Repeat contrast-enhanced computed tomography revealed enlargement of a cystic aortic aneurysm that was present prior to splenectomy. Infected aortic aneurysm was suspected, which was confirmed following thoracic endovascular aortic repair performed on postoperative day 12. DISCUSSION: We consider that splenic rupture occurred following infected of the kidney and spleen by an infected aortic aneurysm. CONCLUSION: Infection should be considered as a cause in patients with atraumatic splenic rupture.

Successful treatment of cervical and upper thoracic esophageal adenocarcinoma using induction chemotherapy followed by surgery: a case report.

Cervical esophageal adenocarcinoma has a low incidence rate and its treatment involves various strategies. We report a patient with locally advanced cervical to upper esophageal adenocarcinoma who was able to undergo induction chemotherapy and radical surgery. A 55-year-old man was diagnosed with a poorly differentiated adenocarcinoma between the cervical and upper thoracic esophagus. The primary lesion had infiltrated into the tracheal membrane and had metastasized into the cervical lymph nodes. The initial diagnosis was T4bN1M1 stage IVB. The lower edge of the tumor was close to the tracheal bifurcation, making it difficult to create a longitudinal tracheal foramen during surgery. Therefore, when biweekly-DCF therapy was performed as induction chemotherapy, the tumor shrank sufficiently and its infiltration into the tracheal membrane decreased subsequently. We performed total laryngopharyngoesophagectomy with three-field lymph node dissection and reconstruction using free jejunal grafts and subtotal stomach via a posterior mediastinum route and a permanent tracheal foramen as a radical surgery. The pathological diagnosis was T2/MP, N1, and the effect of chemotherapy was grade 2. Cervical esophageal adenocarcinoma was rare, but technically reliable and safe oncologic surgery was possible after induction chemotherapy.

The Role of Adjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma Patients with Pathological Positive Lymph Nodes After Neoadjuvant Chemotherapy Followed by Esophagectomy: a Single Institute Retrospective Analysis.

The need for adjuvant therapy after radical resection for patients with stage II-III thoracic esophageal squamous cell carcinoma (TESCC) who have undergone neoadjuvant chemotherapy (NAC) has not been determined. Since recurrence can occur after radical resection and since the prognosis is still poor, it is necessary to consider additional treatment strategies, including adjuvant chemotherapy. We retrospectively investigated the significance of adjuvant therapy after NAC followed by radical resection for TESCC. Between 2008 and 2018, 115 patients with clinical stage II-III underwent radical subtotal esophagectomy after neoadjuvant therapy. Among them, 62 were analyzed, excluding patients with T4 tumors and patients who had undergone R plus resection or who were receiving preoperative chemoradiotherapy. We compared patients who received adjuvant chemotherapy with those who only received observation; we examined overall survival (OS) and recurrence rates. Twenty-nine patients (46.7%) had lymph node metastasis, 12 of whom received adjuvant chemotherapy (41.3%). The recurrence rates for patients with and without lymph node metastasis were 55.1 % and 15.1%, respectively (p = 0.0022). Among patients with lymph node metastasis, there was no significant difference in the recurrence rate (p = 0.9270) or OS (p = 0.5416) based on the administration of adjuvant chemotherapy. However, in 15 patients with two or more positive lymph nodes, adjuvant chemotherapy increased OS (p = 0.0404). Adjuvant chemotherapy was associated with improved OS in clinical stage II-III TESCC patients with two or more pathological positive lymph nodes after NAC followed by radical surgery. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13193-021-01419-0.

Micro-RNA Analysis of Pancreatic Cyst Fluid for Diagnosing Malignant Transformation of Intraductal Papillary Mucinous Neoplasm by Comparing Intraductal Papillary Mucinous Adenoma and Carcinoma.

Although intraductal papillary mucinous neoplasm (IPMN) is thought to be a precursor lesion of pancreatic cancer, diagnosing malignant transformation of IPMN using non-invasive diagnostic methods is difficult and complicated. Micro-RNAs (miRNAs) are currently recognized as biomarkers and molecular targets of various diseases, including malignancy. In this study, we investigated a potential diagnostic approach using miRNA in pancreatic cyst fluid as a marker for evaluating malignant alternation of IPMN. Cystic fluid was sampled mainly during surgical resection. The collected samples were evaluated by performing comprehensive analysis of miRNA using a highly sensitive DNA chip. miRNA expression was compared between IPM adenoma (IPMA) and IPM carcinoma (IPMC) to evaluate the related biomarkers for malignant transformation of IPMN. miRNA analysis revealed that six miRNAs (miR-711, miR-3679-5p, miR-6126, miR-6780b-5p, miR-6798-5p, and miR-6879-5p) in IPMC were significantly enriched compared to those in IPMA. The difference was validated using quantitative real-time PCR. Cyst fluid miRNA analysis might be useful for diagnosing malignant alteration of IPMN. Further evaluations of diagnostic capability as well as functional analysis using the identified miRNAs are required with larger cohorts to confirm its efficacy.

Pancreaticoduodenectomy combined with splenectomy for a patient with pancreatic cancer and pancytopenia due to liver cirrhosis: Case report.

INTRODUCTION AND IMPORTANCE: The incidence of patients with liver cirrhosis (LC) is increasing. Patients with LC are known to have a greater risk of postoperative morbidity and mortality than patients without LC. A treatment option such as pancreaticoduodenectomy (PD) has not been validated to be safe for these patients, especially those with pancytopenia due to portal hypertension (PH). Providing an effective treatment option for these patients is essential. CASE PRESENTATION: Herein, we describe a patient with pancreatic cancer with pancytopenia due to LC that was successfully treated with PD combined with splenectomy. The patient was a 70-year-old woman who was referred to our hospital for evaluation of a mass in the pancreatic head after she developed obstructive jaundice. She was diagnosed with T2N0M0, Stage IB pancreatic cancer and pancytopenia due to PH associated with LC. She received 2 cycles of adjuvant gemcitabine/S-1 chemotherapy and underwent radical subtotal stomach-preserving pancreaticoduodenectomy with splenectomy to improve her pancytopenia. Histopathological examination of the resected specimen revealed an R0 resection showing an Evans grade IIa histological response. Her pancytopenia improved rapidly after surgery. CLINICAL DISCUSSION: Strict indications for PD, haemostatic control of intraoperative bleeding, and optimal perioperative management were important for preventing hepatic decompensation in this patient. Splenectomy is effective for thrombocytopenia due to LC; however, attention to postoperative complications such as overwhelming post-splenectomy infection and portal vein thrombosis is required. CONCLUSION: For patients with pancreatic cancer with pancytopenia due to LC, PD combined with splenectomy plus optimal perioperative management is effective.

Successful treatment of superior mesenteric artery thrombosis via preoperative interventional radiology and surgery using indocyanine green fluorescence.

We report a successful case that offered a symbolic therapeutic experience of interventional radiology and surgery collaboration for superior mesenteric artery thrombosis. A 70-year-old man presented with a chief complaint of sudden abdominal pain. Contrast-enhanced computed tomography revealed superior mesenteric artery thrombosis. Interventional radiology was performed, and thrombotic occlusion was observed in the superior mesenteric artery trunk. The abdominal pain disappeared; however, after a while, the thrombus re-formed and the abdominal pain reappeared. Thus, emergency surgery was performed. Before surgery, thrombus aspiration was performed via interventional radiology as much as possible. During surgery, when the blood flow was evaluated using fluorescence with indocyanine green, a region of markedly poor blood flow was detected in the ileum, and the area was excised. The postoperative course was favorable. In this patient, it is possible that preoperative removal of the thrombus via interventional radiology minimized the ischemic area of the intestinal tract, and blood flow evaluation using indocyanine green allowed reliable excision of only the ischemic area. We believe that our case involved a treatment that exploited the advantages of both interventional radiology and surgery using indocyanine green fluorescence.

Mechanism of acquired 5FU resistance and strategy for overcoming 5FU resistance focusing on 5FU metabolism in colon cancer cell lines.

Fluorouracil (5FU) is converted to its active metabolite fluoro­deoxyuridine monophosphate (FdUMP) through the orotate phosphoribosyl transferase (OPRT)­ribonucleotide reductase (RR) pathway and thymidine phosphatase (TP)­thymidine kinase (TK) pathway and inhibits thymidylate synthase (TS), leading to inhibition of thymidine monophosphate (dTMP) synthesis through a de novo pathway. We investigated the mechanism of 5FU resistance and strategies to overcome it by focusing on 5FU metabolism. Colon cancer cell lines SW48 and LS174T and 5FU­resistant cell lines SW48/5FUR and LS174T/5FUR were used. FdUMP amount was measured by western blotting. The FdUMP synthetic pathway was investigated by combining TP inhibitor (tipiracil hydrochloride; TPI) or RR inhibitor (hydroxyurea; HU) with 5FU. Drug cytotoxicity was observed by crystal violet staining assay. FdUMP was synthesized through the OPRT­RR pathway in SW48 cells but was scarcely synthesized through either the OPRT­RR or TP­TK pathway in SW48/5FUR cells. FdUMP amount in SW48/5FUR cells was reduced by 87% vs. SW48 cells. Expression levels of OPRT and TP were lower in SW48/5FUR when compared with these levels in the SW48 cells, indicating decreased synthesis of FdUMP­led 5FU resistance. These results indicated that fluoro­deoxyuridine (FdU) rather than 5FU promotes FdUMP synthesis and overcomes 5FU resistance. Contrastingly, FdUMP was synthesized through the OPRT­RR and TP­TK pathways in LS174T cells but mainly through the TP­TK pathway in LS174T/5FUR cells. FdUMP amount was similar in LS174T/5FUR vs. the LS174T cells. OPRT and RR expression was lower and TK expression was higher in LS174T/5FUR vs. the LS174T cells, indicating that dTMP synthesis increased through the salvage pathway, thus leading to 5FU resistance. LS174T/5FUR cells also showed cross­resistance to FdU and TS inhibitor, suggesting that nucleoside analogs such as trifluoro­thymidine should be used to overcome 5FU resistance in these cells. 5FU metabolism and mechanisms of 5FU resistance are different in each cell line. Both synthesized FdUMP amount and FdUMP sensitivity should be considered in 5FU­resistant cells.

Inhibition of FGF10-ERK signal activation suppresses intraductal papillary neoplasm of the bile duct and its associated carcinomas.

Evidence regarding intraductal papillary neoplasm of the bile duct (IPNB) as a type of precancerous lesion of cholangiocarcinoma is limited. Moreover, a reproducible in vivo model is lacking, and IPNB pathogenesis remains unclear. Here, we use a doxycycline-inducible tetracycline (Tet)-on mice model to control fibroblast growth factor 10 (FGF10) expression, which regulates branching and tubule formation. FGF10-induced IPNB mimics the multifocal and divergent human IPNB phenotypes via the FGF10-FGF receptor 2 (FGFR2)-RAS-extracellular-signal-regulated kinase (ERK) signaling pathway. A paracrine/autocrine growth factor is sufficient to initiate and maintain IPNB originating from the peribiliary glands, including biliary stem/progenitor cells. With KrasG12D, p53, or p16 mutations or both, Fgf10-induced IPNB shows stepwise carcinogenesis, causing associated invasive carcinoma. Fgf10-induced papillary changes and progression are suppressed by the inhibition of the FGF10-FGFR2-RAS-ERK signaling pathway, demonstrating that the signal is a therapeutic target for IPNB and associated carcinoma.

MYC Up-regulation Is a Useful Biomarker for Preoperative Neoadjuvant Chemotherapy Combined With Anti-EGFR in Liver Metastasis from Colorectal Cancer.

BACKGROUND/AIM: At present, there are no biomarkers to predict the effects of molecular targeted drugs in patients with CRC with liver metastasis. Thus, we performed this study to explore potential biomarkers for these patients. MATERIALS AND METHODS: We obtained cancer tissue specimens from liver metastasis-bearing CRC patients who received the following preoperative neoadjuvant chemotherapies with molecular targeted drugs: i) no therapy (n=3), ii) 5-FU+oxaliplatin+anti-EGFR (n=3), iii) and 5-FU+oxaliplatin+anti-VEGF (n=3). RESULTS: We investigated the RNA expression of 84 genes related to cancer drug resistance using an RT-PCR array. The MYC gene was the only gene that was significantly up-regulated in CRC tissue specimens from anti-EGFR group in comparison to the anti-VEGF group. CONCLUSION: MYC up-regulation in the primary CRC tissues may be a potentially useful biomarker for selecting anti-EGFR combination therapy in neoadjuvant chemotherapy for CRC with liver metastasis.

Splenic artery transposition for hepatic arterial reconstruction in conversion surgery of an initially unresectable, locally advanced pancreatic cancer after gemcitabine/nab-paclitaxel: A case report.

INTRODUCTION AND IMPORTANCE: Recent advances in chemotherapy and chemoradiotherapy allow performance of conversion surgery by improving tumor shrinkage in select patients with initially unresectable locally advanced pancreatic cancer (LAPC), thereby providing curative potential. The number of conversion surgeries requiring arterial reconstruction for select patients with initially unresectable LAPC following favorable responses is expected to increase, so providing effective options for safe arterial reconstruction is critical. CASE PRESENTATION: Herein we report a case of successful conversion surgery for initially unresectable LAPC with splenic artery transposition for hepatic arterial reconstruction after gemcitabine/nab-paclitaxel (GnP). A 71-year-old woman was referred to our hospital for evaluation of a pancreatic head mass after developing diabetes. She was diagnosed with unresectable LAPC, which was in wide contact with the common hepatic artery (CHA), proper hepatic artery (PHA), and splenic artery (SA). She received GnP, and after 6 cycles, durations of disease control and normalization of serum carbohydrate antigen 19-9 (CA19-9) exceeded 7 months. She underwent radical subtotal stomach-preserving pancreaticoduodenectomy with CHA-PHA and portal vein (PV) resection (SA-right hepatic artery anastomosis/PV-superior mesenteric vein direct end-to-end anastomosis). Histopathological examination revealed R0 resection with a histological response of Evans grade IIB. No signs of tumor recurrence have been observed for 14 months postoperatively. CLINICAL DISCUSSION: No consensus has been reached regarding the optimal treatment regimen, duration, or criteria for conversion surgery in patients with LAPC, especially in cases requiring arterial resection. SA transposition for hepatic arterial reconstruction is generally very consistent, easily accessible, and offers adequate length and diameter for successful arterial anastomosis. CONCLUSION: Even for a SA initially in contact with the tumor, SA transposition for hepatic artery reconstruction is a safe and effective option when tumor contact disappears due to chemotherapy.

Feasibility of the Reconstruction with Fascia Lata Patch on the Abdominal Wall Defect After Resection of the Abdominal Desmoid Tumor.

INTRODUCTION: The abdominal desmoid tumor shows invasive development and high local recurrence rate. The primary treatment method is complete removal of the tumor because of the high recurrence rate; however, the problem for the surgeon is the reconstruction of the abdominal wall after resection of the abdominal desmoid tumor. CASE PRESENTATION: A 63-year-old man underwent open drainage and ileostomy for the perforation of ileocecal tumor. After 3 months, he underwent right hemicolectomy and ileostomy closure. Pathological examination revealed no malignancy, and the ileocecal tumor showed the presence of abscess. He noticed a palpable mass in the left abdomen. Enhanced abdominal computed tomography (CT) revealed a large abdominal incisional hernia and an enhanced mass of 40 mm in the left rectus muscle. Needle biopsy was performed and the diagnosis was desmoid tumor. He underwent resection of the desmoid tumor and repair of hernia. We performed wide local resection, with a 2-cm surgical margin. The hernia was repaired by simple closure, and the defect in the left abdomen was repaired with reconstruction using the fascia lata patch through plastic surgery. CONCLUSION: We encountered a case of abdominal wall desmoid tumor combined with a large abdominal incisional hernia. We selected the use of autologous fascia based on the risk of recurrence. The patient has not shown recurrence of incisional hernia or desmoid tumor 22 months after surgery. The use of fascia lata patch can be considered as a satisfactory alternative for such reconstruction cases.

Ascending colon cancer with synchronous right external iliac lymph node metastasis.

A 75-year-old woman was diagnosed with anemia during hospitalization for the treatment of right superior ophthalmic arteriovenous fistula. Colonoscopy revealed an entire circumference of type 2 tumor in the ascending colon. Computed tomography showed ascending colon wall thickening, a tumor with a maximum diameter of 32 mm on the right external iliac artery and multiple low-density nodules in the spleen. We performed right hemicolectomy with D3 lymph node dissection, splenectomy and right external iliac lymph node dissection. Histopathological finding revealed moderately-differentiated adenocarcinoma in ascending colon and right external iliac lymph node. The lesion of spleen was diagnosed as splenic lymphangioma. The patient was discharged on postoperative day 18. Additional treatments, including chemotherapy, were not performed, and no recurrences were seen up to 66 months after surgery. We herein report an uncommon event of ascending colon cancer with synchronous right external iliac lymph node metastasis, which was successfully treated by surgical resection, made feasible when the distant lymph node metastasis is localized.

GelPOINT single-port laparoscopy-assisted transanal minimum invasive surgery for low rectal cancer: a preliminary report on the use of the GOD VISION wireless smart glass-shaped monitor.

BACKGROUND: The GOD VISION wireless smart glass-shaped monitor (INBYTE) was used in the treatment of an elderly patient with mixed breathing disorder undergoing transanal minimally invasive surgery (TAMIS) for low rectal cancer under lumbar anesthesia. METHOD: After wearing the GOD VISION wireless smart glass-shaped monitor, we attached it to the Gel POINT Path® (Applied Medical). The tumor was surgically removed from all layers of the rectum using an ENDOPATH Electrosurgery PROBE PLUS II System® (a spatula-type electric scalpel) and the site was closed after sufficient washing. RESULTS: The total operation time was 93 min, and the estimated blood loss was 6 mL. The patient was discharged without complications on postoperative day 14. No local recurrence or distant metastasis in the 7 months after the operation. The patient remained in a good condition with the preservation of the anal function. CONCLUSIONS: It is necessary to accumulate cases and to perform long-term follow-up. In addition, the anal side operators are able to operate without discomfort. In the present case, the GOD VISION wireless smart glass-shaped monitor allowed the TAMIS operation to be performed more comfortably.

Rectal neuroendocrine tumor developing lateral lymph node metastasis after curative resection: a case report.

BACKGROUND: Among gastrointestinal neuroendocrine tumors (NETs), rectal NETs account for about one-third of all tumors. Despite the occasional observation of lateral lymph node metastasis in patients with rectal NETs, lateral lymph node recurrence is rare. We present a rare case of lateral lymph node recurrence after curative resection of a rectal NET. CASE PRESENTATION: A 55-year-old man presented with fecal occult blood and colonoscopy revealed a mass in the distal rectum. Systematic computed tomography scan showed no evidence of regional lymph node or distant metastasis. The patient underwent laparoscopic intersphincteric resection and D2 lymph node dissection with diverting stoma. Diverting stoma closure was performed 6 months after the initial operation. Pathological diagnosis was NET of the rectum, grade 2, T1b, N0, Stage I without lymphovascular invasion. At 54 months after the surgery, recurrence in a left lateral lymph node was suspected and lymph node dissection was performed. The pathological diagnosis of the specimen was consistent with lateral lymph node metastasis of a recurrent rectal NET. To our best knowledge, there are no case reports in English of lateral lymph node recurrence after curative resection of a rectal NET, grade 2, T1b, N0, Stage I without lymphovascular invasion. CONCLUSION: Considering that patients with lateral lymph node metastasis have worse survival than those without metastasis in rectal cancer, if complete resection of the tumor can be achieved for lateral lymph node recurrence, surgery may be an important option in the strategy to treat this condition.

Intranodal lymphangiography for chyle leakage after esophagectomy: A case report.

Postoperative chylothorax after esophagectomy is a relatively rare complication, but treatment can sometimes be complicated. We report 3 cases of Lipiodol lymphangiography via inguinal lymph node puncture that was effective for chyle leakage occurring after esophagectomy. Case 1: A 67-year-old man with stage IIIA esophageal squamous cell carcinoma underwent radical esophagectomy by video-assisted thoracic surgery (VATS) following neoadjuvant chemotherapy (NAC). After enteral feeding, right pleural effusion drainage increased sharply and changed to white color that was diagnosed as chylothorax. Conservative treatment was started on postoperative day (POD) 15. On POD 50, intranodal Lipiodol lymphangiography and thoracic duct ligation were performed, resulting in complete improvement by the next day. Case 2: A 69-year-old man with stage IIIC esophageal cancer was treated salvage operation following chemoradiation. Postoperative chylothorax was diagnosed on POD 6. Despite conservative treatment, the pleural fluid volume did not decrease. Intranodal Lipiodol lymphangiography performed on POD 13 showed contrast medium draining from the thoracic duct near the tracheal bifurcation. Thoracotomy for thoracic duct ligation was performed on POD 15. Thereafter, drainage from the thoracic drain decreased significantly, and the right thoracic drain was removed 4 days later. Case 3: A 65-year-old man with Stage IVA hypopharyngeal cancer and Stage IIIA esophageal cancer underwent total pharyngopharyngeal esophagectomy by VATS following NAC. Postoperative chylothorax was diagnosed on POD 7. Despite conservative treatment, the pleural fluid volume did not decrease. Intranodal Lipiodol lymphangiography performed on POD 19 completely visualized the thoracic duct and showed no outflow of contrast from the main thoracic duct into the mediastinum. Pleural fluid decreased remarkably after lymphangiography. Intranodal Lipiodol lymphangiography for postoperative chylothorax accurately visualizes flow within the thoracic duct and clearly depicts its positional relationship with other organs. Besides lymphangiography is not only helps to determine the site of chyle leakage but can also be effective for curing chylothorax by less invasive and safer method.

Thoracoscopic subtotal esophagectomy via a right thoracic cavity approach to treat an intractable fistula after 20 months from onset of an idiopathic esophageal rupture: A case report.

An intractable fistula caused by idiopathic esophageal rupture is a rare but severe condition. In the present case, a 69-year-old man had been treated conservatively at another hospital for esophageal rupture but had developed an abscess in the left thoracic cavity due to an intractable fistula at the rupture site. He was referred to our hospital for treatment 19 months after the esophageal rupture. On admission, the intractable fistula was found to be continuous with an abscess in the left thoracic cavity. Preoperative continuous enteral nutrition was administered to improve the patient's nutritional status, and drainage was performed to reduce the size of the abscess. Then, to minimize the invasion of the intractable fistula, thoracoscopic subtotal esophagectomy was performed via a right thoracic cavity approach 20 months after the esophageal rupture. Preoperative management and thoracoscopic surgery via an opposite chest cavity approach was found to be safe and feasible for the intractable fistula caused by idiopathic esophageal rupture.

Risk and early predictive factors of anastomotic leakage in laparoscopic low anterior resection for rectal cancer.

BACKGROUND: In recent years, laparoscopic surgery has been widely used for rectal cancer. In laparoscopic rectal surgery, a double-stapling technique (DST) anastomosis using a stapling device is considered a relatively difficult procedure. Postoperative anastomotic leakage (AL) is a major complication related to patients' quality of life and prognosis. METHODS: This study was a retrospective, single-institution study of 101 rectal cancer patients who underwent laparoscopic low anterior resection (LAR) with DST anastomosis (excluding simultaneous resection of other organs and construction of protective diverting stoma) between February 2008 and November 2017 at the Gifu University Graduate School of Medicine. This study aimed to identify risk and early predictive factors of AL. RESULTS: Among 101 patients, symptomatic AL occurred in 13 patients (12.9%), of whom 10 were male and 3 were female. Their median BMI was 22.7 kg/m2 (range, 17.9-26.4 kg/m2). Among the pre- and intraoperative factors, AL was significantly associated with tumor location (lower rectum), distance from the anal verge (< 6 cm), intraoperative blood loss (≥ 50 ml), and the number of linear staples (≥ 2) in univariate analysis. In multivariate analysis, only intraoperative blood loss (≥ 50 ml, odds ratio [OR] 4.59; 95% confidence interval [CI] 1.04-19.52; p = 0.045) was identified as an independent risk factor for AL. Among the postoperative factors, AL was significantly associated with tachycardia-POD1 (≥ 100 bpm), CRP-POD3 (≥ 15 mg/dl), fever on postoperative day (fever-POD) 3 (≥ 38 °C), and first defecation day after surgery (< POD3) in univariate analysis. In multivariate analysis, fever-POD3 (≥ 38 °C, OR 30.97; 95% CI 4.68-311.22; p = 0.0003) and first defecation day after surgery (< POD3, OR 5.82; 95% CI 1.34-31.30; p = 0.019) were identified as early predictive factors for AL. CONCLUSION: In this study, intraoperative blood loss was an indicator of difficulty in a transection and anastomosing procedure, and fever-POD3 and early first defecation day after surgery were independent early predictive factors for AL. Careful surgery using an appropriate technique and standardized procedures with minimal bleeding and careful postoperative management paying attention to fever and defecation may prevent the onset and severity of AL.

Combination chemotherapy with TAS-102 plus bevacizumab in salvage-line treatment of metastatic colorectal cancer: A single-center, retrospective study examining the prognostic value of the modified Glasgow Prognostic Score in salvage-line therapy of metastatic colorectal cancer.

The combination regimen of TAS-102, a novel oral nucleoside antitumor agent containing trifluridine and tipiracil hydrochloride, with bevacizumab (C-TASK FORCE), a selective monoclonal antibody inhibitor of vascular endothelial growth factor-A, as salvage-line therapy for metastatic colorectal cancer (mCRC) was established based on its high clinical effectiveness. The aim of the present study was to evaluate the prognostic accuracy of the modified Glasgow Prognostic Score (mGPS) in patients receiving TAS-102 plus bevacizumab. The study included 17 patients (12 men and 5 women, mean age 60.4±13.4 years) with unresectable mCRC who were confirmed to have wild-type or mutant RAS genes. The patients received salvage-line treatment with TAS-102 plus bevacizumab at the Surgical Oncology Department of Gifu University School of Medicine between March 2016 and August 2018. The study population was heavily pretreated; the majority of the patients (71%) had received ≥4 prior regimens and, in addition to fluoropyrimidine, irinotecan and oxaliplatin, all had received bevacizumab (100%) and either cetuximab or panitumumab (47%). The RAS status was wild-type in 9 (53%) and mutant in 8 (47%) patients. The primary tumor locations included the right-sided colon in 5 patients (29%; cecum in 2 and transverse colon in 3 cases) and left-sided colorectum in 12 patients [71%; sigmoid colon in 4, rectosigmoid (Rs) in 4, and rectum above/below the peritoneal reflection (Ra/b) in 4 cases]. Metastatic sites included the liver in 15 (88%), lung in 13 (76%), lymph nodes in 7 (41%), and peritoneal dissemination in 5 (24%) patients. The number of metastatic sites was 1 in 3 (18%) and >2 in 14 (82%) patients. Their first staging imaging scans (after 2 cycles of therapy) were available for review in all 17 patients. At first evaluation, 5 (29%) patients had progressive disease (PD), 12 (71%) had stable disease, and none had a partial response to TAS-102 plus bevacizumab. The median overall survival (OS) of 14.1 months and progression-free survival (PFS) of 6.8 months were comparable to the 11.2 and 5.6 months, respectively, in the C-TASK FORCE study. Upon considering three groups, namely mGPS 0, mGPS 1 and mGPS 2, the median PFS times were significantly different (mGPS 0 vs. mGPS 2, P=0.02; and mGPS 1 vs. mGPS 2, P=0.06). The median PFS times in the mGPS 0, 1 and 2 groups were 12.1, 4.8 and 2.3 months, respectively. Median OS was also significantly different (mGPS 0 vs. mGPS 2, P=0.01; and mGPS 1 vs. mGPS 2, P=0.04). The median OS times in the mGPS 0, 1 and 2 groups were 14.0, not reached, and 2 months, respectively. The present study demonstrated the efficacy and safety of the TAS-102 plus bevacizumab combination as salvage-line treatment. This combination therapy (the TAS-102 plus bevacizumab) has obtained valid results with PFS OS as well as C-TASK.FORCE study. The results of the present study also confirmed the prognostic accuracy of mGPS in salvage-line treatment of patients with mCRC.

Diabetic ketoacidosis caused by fulminant type 1 diabetes during adjuvant chemotherapy for colon cancer: A case report.

Development of diabetic ketoacidosis (DKA) caused by fulminant type 1 diabetes (FT1D) during administration of uracil-tegafur (UFT) with leucovorin (LV) as adjuvant chemotherapy is extremely rare. Here, we report a case of DKA caused by FT1D during administration of UFT with LV as adjuvant chemotherapy for colon cancer. A woman in her 60s was transferred to the emergency medical center of our hospital with complaints of impaired consciousness and vomiting. She had undergone left hemicolectomy and D3 lymph node dissection for transverse colon cancer 8 months earlier. She was provided UFT with LV as adjuvant chemotherapy. Laboratory analysis revealed hyperglycemia, high anion gap metabolic acidosis and urinary ketones. She was diagnosed with DKA and was started on intravenous infusion of fluid and continuous subcutaneous insulin injections. Following admission, she was examined and diagnosed with FT1D. The present case describes an extremely rare case of DKA caused by FT1D during adjuvant chemotherapy with UFT + LV for colon cancer.