Rare recurrence pattern after complete response to chemotherapy in a patient with rectal cancer: a case report.

BACKGROUND: Colorectal cancer (CRC) often metastasizes to the liver, lungs, lymph nodes, and peritoneum but rarely to the bladder, small intestine, and skin. We here report the rare metastasis of anal cancer in the left bladder wall, followed by metastases to the small intestine and skin, after abdominoperineal resection and left lateral lymph node dissection with chemotherapy in a patient with clinician Stage IVa disease. CASE PRESENTATION: A 66-year-old man presented with 1-month history of bloody stool and anal pain and diagnosed with clinical Stage IVa anal cancer with lymph node and liver metastases (cT3, N3 [#263L], M1a [H1]). Systemic chemotherapy led to clinical complete response (CR) for the liver metastasis and clinical near-CR for the primary tumor. Robot-assisted laparoscopic perineal rectal resection and left-sided lymph node dissection were performed. Computed tomography during 18-month postoperative follow-up identified a mass in the left bladder wall, which was biopsied with transurethral resection, was confirmed as recurrent anal cancer by histopathologic evaluation. After two cycles of systemic chemotherapy, partial resection of the small intestine was performed due to bowel obstruction not responding to conservative therapy. The histopathologic evaluation revealed lymphogenous invasion of the muscularis mucosa and subserosa of all sections. Ten months after the first surgery for bowel obstruction and two months before another surgery for obstruction of the small intestine, skin nodules extending from the lower abdomen to the thighs were observed. The histopathologic evaluation of the skin biopsy specimen collected at the time of surgery for small bowel obstructions led to the diagnosis of skin metastasis of anal cancer. Although panitumumab was administered after surgery, the patient died seven months after the diagnosis of skin metastasis. CONCLUSIONS: This case illustrates the rare presentation of clinical Stage IVa anal cancer metastasizing to the bladder wall, small intestine, and skin several years after CR to chemotherapy.

[A Case of Conversion Surgery for Unresectable Advanced Gastric Cancer of Which Metastatic Site Was Disappear by Chemotherapy but the Primary Site Was Enlarged after Five Years].

A 77-year-old man presented to our hospital with a chief complaint of stomachache. He received a diagnosis of unresectable advanced gastric cancer classified as cT3, N+, M1(LYM, HEP, OSS), Stage ⅣB. He underwent first-line chemotherapy with SOX, second-line treatment with PTX plus Ram, and third-line treatment with nivolumab. The primary tumor showed a reduction in size, and liver and lymph node metastases were not detectable. However, after 5 years of chemotherapy, a re- enlargement was observed in the primary gastric lesion without progression of liver and lymph node metastases. Subsequently, conversion surgery was performed. Based on the pathological analysis, the diagnosis was ypT1b2(SM2), N0(0/17), M0, ypStage ⅠA, R0. After nivolumab administration postoperatively for 5 months, chemotherapy was discontinued as there was no recurrence.

Cross-coupling of organic fluorides with allenes: a silyl-radical-relay pathway for the construction of α-alkynyl-substituted all-carbon quaternary centres.

Controlling the transformation of versatile and reactive allenes is a considerable challenge. Herein, we report an efficient silylboronate-mediated cross-coupling reaction of organic fluorides with allenes to construct a series of sterically demanding α-ethynyl-containing all-carbon quaternary centers (ACQCs), using catalyst-free silyl-radical-relay reactions to selectively functionalize highly inert C-F bonds in organic fluorides. The key to the success of this transformation lies in the radical rearrangement of an in situ-generated allenyl radical to form a bulky tertiary propargyl radical; however, the transformation does not show efficiency when using the propargyl isomer directly. This unique reaction enables the cross-coupling of a tertiary carbon radical center with a C(sp2)-F bond or a benzylic C(sp3)-F bond. α-Ethynyl-containing ACQCs with (hetero)aromatic substituents and benzyl were efficiently synthesized in a single step using electronically and sterically diverse organic fluorides and allenes. The practical utility of this protocol is showcased by the late-stage functionalization of bioactive molecules and the modification of a liquid crystalline material.

Clinical Impact of Transanal Drainage Tube on Anastomosis Leakage Following Minimally Invasive Resection Without Diverting Stoma in Patients With Rectal Cancer: A Propensity Score-matched Analysis.

OBJECTIVES: As one of the most serious complications of rectal cancer (RC) surgery, preventing anastomotic leakage (AL) is crucial. Several studies have suggested a positive role of the transanal drainage tube (TaDT) in AL prevention. However, whether TaDT is beneficial for AL in patients with RC remains controversial. The present study aimed to evaluate the clinical impact of TaDT on AL following minimally invasive resection without diverting stoma (DS) in patients with RC. MATERIALS AND METHODS: We retrospectively analyzed 392 consecutive patients with RC who had undergone minimally invasive resection without DS between 2010 and 2021. Propensity score matching (PSM) was performed to reduce selection bias. AL was classified as grade A, B, or C. RESULTS: A TaDT was used in 214 patients overall. After PSM, we enrolled 316 patients (n=158 in each group). Before PSM, significant group-dependent differences were observed in terms of age, American Society of Anesthesiologists physical status, and the use of antiplatelet/anticoagulant agents. The frequency of AL was 7.3% in the overall cohort and was significantly lower in the TaDT group (3.7%) than in the non-TaDT group (11.8%). The rate of grade B AL was significantly lower in the TaDT group than in the non-TaDT group (before PSM, P <0.01; after PSM, P =0.02). However, no significant differences between groups were found for grade C AL. Moreover, multivariate analysis identified the lack of a TaDT as an independent risk factor for AL in the overall and matched cohorts [before PSM, odds ratio, 3.64, P <0.01; after PSM, odds ratio, 2.91, P =0.02]. CONCLUSION: These results indicated that TaDT may play a beneficial role in preventing AL, particularly of grade B, for patients with RC undergoing minimally invasive resection without DS. However, further randomized controlled trials, including patient-reported outcomes, are still needed to understand better the role of TaDT in preventing ALs in patients with RC undergoing minimally invasive resection without DS.

Aggressive surgical intervention may improve prognosis in patients with ovarian metastasis from colorectal cancer.

PURPOSE: The current study aimed to investigate the prognostic clinicopathological factors of synchronous and metachronous ovarian metastasis (OM) from colorectal cancer (CRC) in patients with and without oophorectomy. METHODS: Female patients with OM from CRC who underwent primary tumor resection at our institution from January 2013 to December 2020 were evaluated. RESULTS: Of 661 female patients, 22 (3.3%) were diagnosed with OM. Among 22 patients with OM, 12 underwent OM resection. Twenty (91%) patients had extra OM upon diagnosis. Thirteen (59%) patients in the non-surgery group had peritoneal dissemination at surgery or on computed tomography scan or positron emission tomography-computed tomography. Two patients in the OM surgery group had emergency surgery because of abdominal pain. Four patients had postoperative complications, and the median duration of hospital admission was 16.5 days. The median survival time from OM diagnosis to mortality was 20.9 months. Then, the association between the clinicopathological factors and overall survival (OS) was investigated. Tumor location and surgery were found to be related to OS (p = 0.03, 0.006, respectively) in the univariate analysis. However, only surgery was associated with OS (p = 0.02) in the multivariate analysis. CONCLUSION: Surgery is an important prognostic clinicopathological factor of OM from CRC. OM tumors should be resected because OM surgery is less likely to cause complications and symptoms.

Regio- and Z-Selective Alkyne Hydroamination and Hydrophenoxylation using Tetrafluoro-λ6 -Sulfanyl Alkynes under Superbasic, Naked Anion Conditions.

Alkyne hydroamination is an effective approach for the production of enamines and enamine-containing N-heterocycles. However, stereoselectivity control is a considerable challenge in this reaction because of the electronic repulsion between an incoming nitrogen lone pair and the alkyne π-system. Herein, we propose a methodology involving ß-regio- and Z-selective alkyne hydroamination by using tetrafluoro-λ6 -sulfanyl (SF4 ) alkynes under superbasic, naked anion conditions. The reaction is compatible with a wide variety of N-heterocycles, including indoles, carbazoles, pyrazoles, and imidazoles, and selectively furnishes SF4 -linked Z-vinyl enamines with ß-regioselectively. Moreover, the method can be extended to the ß- and Z-controlled, base-mediated alkyne hydrophenoxylation with phenols to provide SF4 -linked Z-vinyl ethers in high yields. As the SF4 unit has attracted attention as a bioisostere for alkynes, p-benzenes, bicyclo[1.1.1]pentyl (BCP) groups, and cubanes in medicinal chemistry, this chemistry represents an effective approach to creating novel drug candidates incorporating SF4 -containing molecules.

Elemental Sulfur-Mediated Transformation of Carboxylic Acids to Acyl Fluorides by Electrophilic Fluorinating Reagent, Selectfluor.

The elemental sulfur-mediated synthesis of acyl fluorides from carboxylic acids is achieved using Selectfluor. A broad range of acyl fluorides are accessible from carboxylic acids while avoiding the formation of acid anhydrides. 19F NMR spectra suggest that S8-fluoro-sulfonium cation A and neutral S8-difluoride A' generated in situ are the reactive species in this deoxyfluorination reaction.

Single-incision laparoscopic surgery for intestinal intussusception due to neuroendocrine tumor.

BACKGROUND: Small intestinal neuroendocrine tumor (NET) is uncommon, but intestinal intussusception caused by NET is even rare. We report a rare case of single-incision laparoscopic surgery (SILS) for intestinal intussusception due to NET G1. CASE PRESENTATION: A 72-year-old woman presented with vomiting, diarrhea, and abdominal pain. Contrast-enhanced computed tomography (CT) revealed the target sign in the ascending colon. An enhanced nodule was detected at the lead point, leading us to suspect a tumor. Colonoscopy showed a tumor at the lead point of the intestinal intussusception. Histological findings led to a diagnosis of NET G1. Single-incision laparoscopic ileocecal resection with regional lymphadenectomy was then performed. The patient was discharged 10 days postoperatively with no complications. CONCLUSION: We achieved SILS with regional lymphadenectomy for preoperatively diagnosed intestinal intussusception due to NET G1. Although this condition is rare, surgeons should take this possibility into consideration in cases showing similar findings.

Oncological outcomes following minimally invasive surgery for pathological N2M0 colorectal cancer: A propensity score-matched analysis.

INTRODUCTION: Whether minimally invasive surgery (MIS) is safe and effective for patients with N2M0 colorectal cancer (CRC) remains controversial. This study aimed to compare short- and long-term outcomes between MIS and open surgery (Open) groups for patients with pathological (p)N2M0 CRC, and evaluate the oncological outcomes of MIS for pN2M0 CRC. MATERIALS AND METHODS: We retrospectively analyzed 125 consecutive patients with pN2M0 CRC who underwent curative surgery between 2010 and 2017, using propensity score-matching (PSM) analysis. RESULTS: Median follow-up was 59.4 months. After PSM, we enrolled 68 patients (n = 34 in each group). The conversion rate was 9.6% for the entire patient cohort and 5.9% for the matched cohort. In colon cancer (CC), short-term outcomes were similar between groups. On the other hand, in rectal cancer (RC), estimated blood loss, rate of anastomosis leakage, and length of postsurgical stay were lower in the MIS group than the Open group. R0 resection was achieved in all patients with MIS. No surgical mortality was encountered in any group. No significant differences were found between groups in terms of 3-year local recurrence rate, overall survival, cancer-specific survival, or recurrence-free survival among the entire patient cohort or the matched cohort, regardless of the primary tumor site (CC or RC). Surgical approach (MIS vs Open) had no significant influence on survival outcomes. CONCLUSIONS: MIS is a safe and effective option for patients with pN2M0 CRC, with acceptable short- and long-term outcomes comparable to the open approach. MIS can be considered for patients with pN2M0 CRC.

A case in which the ileocolic vein draining into the gastrocolic trunk of Henle could be diagnosed preoperatively: a rare anatomical case report.

BACKGROUND: Numerous variations in vascular anatomy have been reported in the right colon. The ileocolic vein (ICV) generally drains directly into the superior mesenteric vein (SMV), and is an important landmark for laparoscopic surgery in right colon cancer. We present here a patient with a vascular anomaly of the ICV that was diagnosed on preoperative imaging. CASE PRESENTATION: A 65-year-old woman was diagnosed with transverse colon cancer by colonoscopy. Preoperative computed tomography scan showed that the ICV drained into the gastrocolic trunk of Henle (GCT) rather than the SMV. Single-incision laparoscopic transverse colectomy with D3 lymph node dissection was performed, dividing the middle colic vein (MCV) and preserving the right gastroepiploic vein (RGEV), anterior superior pancreaticoduodenal vein (ASPDV), GCT and ICV. The intraoperatively identified venous anatomy was consistent with the preoperative evaluation, and the RGEV, ASPDV and ICV were found to form the GCT. CONCLUSION: We report a rare vascular anatomical anomaly that was diagnosed preoperatively, facilitating safe and successful single-incision laparoscopic surgery with D3 lymph node dissection.

Regioselective Synthesis of Pyridine-SF4-Methyl Ketones via Hydration of Pyridine-SF4-Alkynes.

Herein, we report the metal-free hydration of pyridine-SF4-alkynes, under acidic conditions and with reaction durations ranging from 5 min to 10 h at room temperature, to synthesize pyridine-SF4-methyl ketones in yields of 59-93%. Further, we demonstrate the synthetic applications of the synthesized pyridine-SF4-methyl ketones, such as chlorination, NaBH4 reduction, Baeyer-Villiger oxidation, and the generation of enol-triflates. These compounds hold promise as useful building blocks in the syntheses of a wide range of SF4-containing drug candidates.

[Outcome of Hepatectomies for Non-Colorectal Liver Metastases].

We performed 16 cases of non-colorectal liver metastasis resection(19 resections)between January 2011 and December 2021. Among the 16 cases, the primary lesions were as follows: gastric cancer in 7 cases; GIST in 2 cases; and neuroendocrine tumor, renal cancer, pancreatic cancer(acinic cell carcinoma), cholangiocarcinoma, breast cancer, ovarian cancer, and leiomyosarcoma in 1 case each. The median time from primary lesion resection to the diagnosis of liver metastasis was 20.6 months. In cases of neuroendocrine tumors and renal cancer, hepatectomy was performed with a preoperative diagnosis of hepatocellular carcinoma. Four cases underwent laparoscopic hepatectomy, and 10 cases underwent anatomical liver resection. Postoperative chemotherapy was performed in 8 cases. Recurrence of liver metastasis was observed in 7 cases. One case of gastric cancer and 1 case of neuroendocrine tumor underwent repeat hepatectomy. The median relapse-free survival was 13.8 months, and the median overall survival was 55.7 months.

[A Case of Synchronous Secondary Lymph Node Metastasis in the Mesentery of the Ileum with cCR Achievement after Surgery for Sigmoid Colon Cancer].

A 71-year-old woman was hospitalized with loose stools and lightheadedness. She was subsequently diagnosed with sigmoid colon cancer for which we performed a laparoscopic sigmoid colectomy, small intestine partial resection, partial bladder resection, and open conversion. The intraoperative findings and histopathological analysis showed secondary lymph node metastasis in the mesentery of the ileum, and the surgery resulted in R2 resection. Chemotherapy(CAPOX plus Bev) was initiated thereafter, and the L-OHP and Bev were discontinued over time. A complete response was achieved at 1 year postoperative. Capecitabine alone was continued, and no signs of recurrence were noted at 2 years postoperative.

[A Case of Resection of Sigmoid Colon Metastasis from Pancreatic Cancer].

A 73-year-old man underwent distal pancreatectomy for invasive pancreatic ductal carcinoma in 2018. He showed stenosis of sigmoid colon due to recurrence of pancreatic cancer and received transverse colostomy in 2020. One year after initiation of gemcitabine monotherapy, he complained of abdominal pain. CT images and colonoscopy revealed accumulation of mucus in sigmoid colon due to stenotic lesions. Because conservative treatment using antibiotics was not effective, we performed sigmoidectomy. Histological examination revealed that tubular adenocarcinoma located mainly in the muscularis propria invaded into the colonic mucosa. Immunohistochemical analysis showed positive staining for CK7, and negative for CK20. We diagnosed sigmoid colon metastases of pancreatic cancer.

[Metachronous Ovarian Metastasis of Colorectal Cancer at Our Hospital].

Among the cases that underwent primary tumor resection(PTR)of colorectal cancer at our hospital between January 2010 and December 2020, we examined 6 cases that involved ovarian metastasis(OM)surgery. The period from PTR to recurrence of OM was 2-28 months. Bilateral oophorectomy or bilateral salpingo-oophorectomy was performed in 5 cases, and unilateral oophorectomy was performed in 1. The reasons for surgery were symptom development and progressive disease. The period from recurrence of OM to OM surgery was short, that of 0-6 months. In 5 cases, peritoneal dissemination and other distant metastases were observed during OM surgery; R0 resection was performed in 2 cases. Postoperative complications associated with OM surgery were not observed. The median time required from the day of OM surgery to the resumption of chemotherapy was 33 days, and it was possible to resume chemotherapy early. The median survival time after OM surgery was approximately 11 months, which is considered to be owing to the influence of complications of peritoneal dissemination and other distant metastases.

[A Resected Case of the Sigmoid Colon Cancer after the Endovascular Aneurysm Repair in Which Intraoperative Indocyanine Green Fluorescence Method Was Useful for Evaluating the Blood Flow in the Colon].

A man in his 70s underwent an endovascular aneurysm repair(EVAR)for abdominal aortic aneurysm. Blood test revealed an anemia and an increased tumor marker. Enhanced computed tomography revealed the wall thickening in the sigmoid colon and the Type Ⅱ endoleak after EVAR. Colonoscopy showed the wall thickening in the sigmoid colon, and biopsy indicated a diagnosis of adenocarcinoma. We performed open sigmoid colectomy with D3 lymph node dissection and ileostomy. We performed intraoperative indocyanine green (ICG) fluorescence method for evaluating the blood flow in the colon before the high ligation of the inferior mesenteric artery and the creation of the anastomosis, and perfusion of the colon was visualized. He was discharged postoperative day 14, and was performed closure of ileostomy 5 months later. Intraoperative ICG fluorescence method was safety and useful for evaluating the blood flow in the colon.

Inhibition of c-MET reverses radiation-induced malignant potential in pancreatic cancer.

As a treatment option for PDAC, radiation therapy induces good local control. However, radiation also reportedly enhances the malignant potential (e.g., invasion and migration ability) in various cancers, thus increasing the risk of distant metastasis. It remains unclear how radiation induces malignant potential, and how such enhanced malignant potential can be suppressed. In the current study, we evaluated the sequential change of c-Met expression in pancreatic cancer cells following irradiation. We found that irradiation transiently induced c-Met expression in vitro. In an in vivo subcutaneous tumor mouse model, irradiation also enhanced downstream phosphorylated Met (p-Met). Furthermore, this enhancement of p-Met protein expression was suppressed by oral administration of the c-Met inhibitor INC280. Irradiated pancreatic cancer cells with enhanced c-Met expression exhibited higher malignant potential, including invasion and migration ability, compared with cells showing low c-Met expression. Pancreatic cancer cells that overexpressed c-met also showed enhanced malignant potential, which was reversed by c-Met inhibition. Additionally, c-Met inhibitor suppressed the metastatic potential in a liver metastasis mouse model using c-met-overexpressing cells. Overall, our present results revealed that irradiation could induce c-met expression in pancreatic cancer cells, leading to enhanced malignant potential (e.g., invasion and migration ability) and thus promoting distant metastasis. Moreover, a c-Met inhibitor could reverse this enhanced malignant potential.

Identification of fucosylated haptoglobin-producing cells in pancreatic cancer tissue and its molecular mechanism.

Fucosylated haptoglobin is a well-established glyco-biomarker of pancreatic cancer. We recently established a novel anti-glycan antibody (10-7G mAb) that specifically recognizes fucosylated haptoglobins, including prohaptoglobin (proHpt). Serum concentrations of the 10-7G value, as measured by ELISA, were increased in patients with pancreatic cancer relative to the healthy controls. However, it is currently unknown which specific tissue or cell type produces fucosylated haptoglobins or proHpt. In the present study, we performed immunohistochemical (IHC) and ELISA analyses of pancreatic cancer tissue samples using 10-7G mAb. Among 21 pancreatic tissue sections, only 1 showed direct staining of pancreatic cells with the 10-7G mAb. However, 12 of the 21 sections stained positively for immune cells. Although there was no significant difference in the 10-7G expression between the positive and negative staining IHC groups, the median value of serum 10-7G was slightly higher in IHC-positive cases. Among many assayed leukemic cell lines, differentiated THP-1 cells (a human acute monocytic leukemia cell line) were found to have the highest levels of proHpt, per Western blot using 10-7G mAb. Interestingly, production of proHpt in vitro was dramatically increased under either hypoxic conditions or after IL-6 treatment. These results suggest that immune cells, including macrophages, in the pancreatic tissue microenvironment produce fucosylated haptoglobin and proHpt. Thus, fucosylated haptoglobins can be detected by the 10-7G mAb and may be a promising biomarker for pancreatic cancer.

CKAP4, a DKK1 Receptor, Is a Biomarker in Exosomes Derived from Pancreatic Cancer and a Molecular Target for Therapy.

PURPOSE: The survival rate of pancreatic ductal adenocarcinoma (PDAC) is poor; thus, novel molecularly targeted therapy and companion diagnostics are required. We asked whether cytoskeleton-associated protein 4 (CKAP4), a novel Dickkopf1 (DKK1) receptor, is a candidate for PDAC diagnosis and therapy.Experimental Design: Whether CKAP4 can be secreted with small extracellular vesicles (SEV) from PDAC cells was examined. It was also investigated whether CKAP4 can be detected in sera from patients with PDAC by ELISA using newly generated anti-CKAP4 mAbs and whether anti-CKAP4 mAbs can show antitumor activity in vivo. RESULTS: CKAP4 was secreted with SEVs from PDAC cells, and the SEVs exhibited the characteristics of exosomes. The secretion of CKAP4-containing exosomes was mediated by DKK1-dependent endocytosis routes and required exosome biogenesis molecules. Two ELISAs capable of detecting tumor-secreted CKAP4 were developed. The serum CKAP4 levels were higher in patients with PDAC than healthy control individuals. CKAP4 was highly detected in the sera of pancreatic tumor-bearing xenografted mice and patients with PDAC, whereas CKAP4 was barely detectable in sera from normal mice and postoperative patients. Anti-CKAP4 mAbs with different epitopes demonstrated the inhibitory activities for the binding of DKK1 and CKAP4, AKT activity, and proliferation and migration of PDAC cells. Anti-CKAP4 mAbs also suppressed xenograft tumor formation in immunodeficient mice and extended the survival of mice receiving intraperitoneal or orthotopic injection of PDAC cells. CONCLUSIONS: CKAP4 secreted in exosomes may represent a biomarker for PDAC. Anti-CKAP4 mAbs can contribute to the development of novel diagnostic methods and therapeutics.