Nephrocolocutaneous fistula from a staghorn calculus.

Fistula formation between the kidney, colon and the skin is an extremely rare complication arising from renal infections secondary to renal stone formation. During the 1980s, reports of nephrocolic fistulas, with or without involvement of the skin, were commonly caused by genitourinary tuberculosis. Due to improvements in diagnosis and specifically the development of anti-Koch's therapy, the incidence of nephrocolic or nephrocolocutaneous fistulas has become uncommon especially in developed countries.We report a case of a patient residing in a developing country, presenting with a 20-year history of a left flank lesion extruding minimal purulent output daily. He was seen at the emergency department due to weakness and was managed as a case of urosepsis. Contrast-enhanced CT scan and fistulogram showed a staghorn calculus in the left kidney with connections to the descending colon and skin. The patient eventually underwent a left hemicolectomy with en bloc excision of the kidney and fistula tract.

Surgical Management of Patients With GI Tuberculosis.

BACKGROUND: The Philippines ranks 10th in tuberculosis prevalence worldwide. Aside from pulmonary tuberculosis, GI tuberculosis remains an important cause of morbidity and mortality, particularly in endemic areas. OBJECTIVE: This study aimed to describe the clinicopathologic profile and surgical outcomes of patients with GI tuberculosis. DESIGN: Retrospective descriptive study. SETTING: Department of Surgery at the Philippine General Hospital, Manila, Philippines. PATIENTS: This study included all newly diagnosed cases of GI tuberculosis from January 1, 2009, to December 31, 2019. MAIN OUTCOME MEASURES: Clinical response to surgery. RESULTS: A total of 241 confirmed new cases were managed during an 11-year period. Of these, 208 patients (86.30%) underwent outright surgery, whereas the remaining patients (13.69%) received antituberculous therapy. Fifteen medically managed patients eventually required surgery, bringing the total surgically managed patients to 223. The patients' age ranged from 19 to 72 years, with a 1.9:1 male to female ratio. The most common complaint was abdominal pain. Intestinal obstruction was the most common indication for surgery. A right hemicolectomy was the most often performed procedure, with the ileocecal area as the most frequently involved segment. The most common histopathologic findings were epithelioid granuloma and caseation necrosis. Postoperative length of stay ranged from 0 to 59 days (mean, 7 days). Morbidity rate was 5.38% and mortality rate was 3.14%. Four deaths were operative and resulted from septic shock because of hollow viscus perforation. LIMITATIONS: This study was limited to histopathologic basis for diagnosis. CONCLUSION: The recommended initial therapy for all forms of extrapulmonary tuberculosis is a 6-month regimen of antituberculous therapy unless the organisms are known or suspected to be resistant to first-line drugs. Surgery is reserved for complications of intra-abdominal tuberculosis: obstruction, perforation, or severe bleeding. Timely surgical intervention, coupled with medical management led to the best outcomes for these patients. See Video Abstract at http://links.lww.com/DCR/C56. MANEJO QUIRRGICO DE PACIENTES CON TUBERCULOSIS GASTROINTESTINAL: ANTECEDENTES:Las Filipinas ocupa el décimo lugar en prevalencia de tuberculosis en todo el mundo. Aparte de la tuberculosis pulmonar, la tuberculosis gastrointestinal sigue siendo una causa importante de morbilidad y mortalidad, especialmente en las zonas endémicas.OBJETIVO:Este estudio tuvo como objetivo describir el perfil clinicopatológico y los resultados quirúrgicos de pacientes con tuberculosis gastrointestinal.DISEÑO:Estudio descriptivo retrospectivo.AJUSTE:Departamento de Cirugía del Hospital General de Filipinas, Manila, Filipinas.PACIENTES:Todos los casos de tuberculosis gastrointestinal recién diagnosticados desde el 1 de Enero del 2009 hasta el 31 de Diciembre del 2019.MEDIDAS DE RESULTADO PRINCIPAL:Respuesta clínica a la cirugía.RESULTADOS:Se manejaron un total de 241 casos nuevos confirmados durante un período de 11 años. De estos, 208 (86,30%) pacientes fueron intervenidos directamente quirúrgicamente mientras que el resto recibió tratamiento antituberculoso (13,69%). Quince pacientes manejados médicamente finalmente requirieron cirugía, lo que elevó el total de pacientes manejados quirúrgicamente a 223. Las edades de los pacientes oscilaron entre 19 y 72 años, con una proporción de 1,9: 1 entre hombres y mujeres. La queja más común fue el dolor abdominal. La obstrucción intestinal fue la indicación más frecuente para cirugía. La hemicolectomía derecha fue el procedimiento más realizado, siendo la zona ileocecal el segmento más afectado. Los hallazgos histopatológicos más comunes fueron granuloma epitelioide y necrosis caseosa. La estancia postoperatoria varió de 0 a 59 días (media, 7 días). Las tasas de morbilidad y mortalidad fueron 5,38% y 3,14%, respectivamente. Cuatro fueron muertes operatorias por choque séptico debido a perforación de víscera.LIMITACIONES:Este estudio se limitó a la base histopatológica para el diagnóstico.CONCLUSIÓN:La terapia inicial recomendada para todas las formas de tuberculosis extrapulmonar es un régimen de 6 meses de terapia antituberculosa a menos que se sepa o se sospeche que los organismos son resistentes a los medicamentos de primera línea. La cirugía se reserva para las complicaciones de la tuberculosis intraabdominal, es decir, obstrucción, perforación o hemorragia grave. La intervención quirúrgica oportuna, junto con el manejo médico, condujo a mejores resultados para estos pacientes. Consulte el Resumen del Video en http://links.lww.com/DCR/C56. (Traducción- Dr. Yesenia Rojas-Khalil).

MARCKS as a Potential Therapeutic Target in Inflammatory Breast Cancer.

Inflammatory breast cancer (IBC) is the most pro-metastatic form of breast cancer (BC). We previously demonstrated that protein overexpression of Myristoylated Alanine-Rich C Kinase Substrate (MARCKS) protein was associated with shorter survival in IBC patients. MARCKS has been associated with the PI3K/AKT pathway. MARCKS inhibitors are in development. Our objective was to investigate MARCKS, expressed preferentially in IBC that non-IBC (nIBC), as a novel potential therapeutic target for IBC. The biologic activity of MPS, a MARCKS peptide inhibitor, on cell proliferation, migration, invasion, and mammosphere formation was evaluated in IBC (SUM149 and SUM190) and nIBC (MDA-MB-231 and MCF7) cell lines, as well as its effects on protein expression in the PTEN/AKT and MAPK pathways. The prognostic relevance of MARCKS and phosphatase and tensin homolog (PTEN) protein expression as a surrogate marker of metastasis-free survival (MFS) was evaluated by immunohistochemistry (IHC) in a retrospective series of archival tumor samples derived from 180 IBC patients and 355 nIBC patients. In vitro MPS impaired cell proliferation, migration and invasion, and mammosphere formation in IBC cells. MARCKS inhibition upregulated PTEN and downregulated pAKT and pMAPK expression in IBC cells, but not in nIBC cells. By IHC, MARCKS expression and PTEN expression were negatively correlated in IBC samples and were associated with shorter MFS and longer MFS, respectively, in multivariate analysis. The combination of MARCKS-/PTEN+ protein status was associated with longer MFS in IBC patient only (p = 8.7 × 10-3), and mirrored the molecular profile (MARCKS-downregulated/PTEN-upregulated) of MPS-treated IBC cell lines. In conclusion, our results uncover a functional role of MARCKS implicated in IBC aggressiveness. Associated with the good-prognosis value of the MARCKS-/PTEN+ protein status that mirrors the molecular profile of MPS-treated IBC cell lines, our results suggest that MARCKS could be a potential therapeutic target in patients with MARCKS-positive IBC. Future preclinical studies using a larger panel of IBC cell lines, animal models and analysis of a larger series of clinical samples are warranted in order to validate our results.

Serum lactate and acute mesenteric ischaemia: An observational, controlled multicentre study.

BACKGROUND: Early diagnosis and prompt management of acute mesenteric ischaemia (AMI) are key to survival but remain extremely difficult, due to vague and non-specific symptoms. Serum lactate (SL) is commonly presented as a useful biomarker for the diagnosis or prognosis of AMI. The aim of our study was test SL (1) as a diagnostic marker and (2) as a prognostic marker for AMI. STUDY DESIGN: This was an ancillary multicentre case-control study. Patients with AMI at intensive care unit (ICU) admission were included (AMI group) and matched to ICU patients without AMI (control group). SL was measured and compared on day 0 (D0) and day 1 (D1). Diagnosis and prognosis accuracy were assessed by receiver operating characteristic (ROC) and their area under the curve (AUC). RESULTS: Each group consisted of 137 matched ICU patients. There was no significant difference of SL between the two groups at D0 or at D1 (p = 0.26 and p = 0.29 respectively). SL was a poor marker of AMI: at D0 and D1, AUC were respectively 0.57 [0.51; 0.63] and 0.60 [0.53; 0.67]. SL at D0 and D1 correctly predicted ICU mortality, independently of AMI (AUC D0: 0.69 [0.59; 0.79] vs. 0.74 [0.65; 0.82]; p = 0.51 and D1: 0.74 [0.64; 0.84] vs. 0.76 [0.66; 0.87]; p = 0.77, respectively, for control and AMI groups]. CONCLUSIONS: SL has no specific link with AMI, both for diagnosis and prognosis. SL should not be used for the diagnosis of AMI but, despite its lack of specificity, it may help to assess severity.

Perianal basal cell carcinoma managed with wide excision and random flap reconstruction.

Basal cell carcinoma (BCC) is a common skin malignancy and usually occurs in sun-exposed areas like the head and neck. Occurrence in the perianal area is rare, accounting for only 0.08% of all BCC, and 0.2% of anorectal malignancies.We present a case of a hypertensive woman in her 60s who had a 1-year history of a gradually enlarging mass on the left perianal region. Initial biopsy revealed a carcinoma with basaloid features and was confirmed on immunohistochemistry to be nodular BCC. Proctoscopy showed no intraluminal involvement. Contrast-enhanced chest and abdominal CT scans revealed no nodal or distant metastasis. MRI showed a 7.5 mm fat plane between the mass and the external sphincter muscles, projecting adequate surgical margins.A wide excision with at least 4 mm margins was performed. Reconstruction of the resulting defect was performed with a local random cutaneous flap.

Overcoming Resistance to Anti-Nectin-4 Antibody-Drug Conjugate.

Antibody-drug conjugates (ADC) represent a fast-growing drug class in oncology. However, ADCs are associated with resistance, and therapies able to overcome it are of utmost importance. Recently, enfortumab vedotin-ejfv (EV) was approved in nectin-4+ metastatic urothelial cancer. We previously described PVRL4/nectin-4 as a new therapeutic target in breast cancer and produced an efficient EV-like ADC comprising a human anti-nectin-4 mAb conjugated to monomethyl auristatin-E (MMAE) named N41mab-vcMMAE. To study the consequence of the long-term treatment with this ADC, we developed a preclinical breast cancer model in mice, and report a mechanism of resistance to N41mab-vcMMAE after 9-month treatment and a way to reverse it. RNA-sequencing pointed to an upregulation in resistant tumors of ABCB1 expression, encoding the multidrug resistance protein MDR-1/P-glycoprotein (P-gp), associated with focal gene amplification and high protein expression. Sensitivity to N41mab-vcMMAE of the resistant model was restored in vitro by P-gp pharmacologic inhibitors, like tariquidar. P-gp is expressed in a variety of normal tissues. By delivering the drug to the tumor more specifically than classical chemotherapy, we hypothesized that the combined use of ADC with P-gp inhibitors might reverse resistance in vivo without toxicity. Indeed, we showed that the tariquidar/N41mab-vcMMAE combination was well tolerated and induced a rapid regression of ADC-resistant tumors in mice. In contrast, the tariquidar/docetaxel combination was toxic and poorly efficient. These results show that ABC transporter inhibitors can be safely used with ADC to reverse ADC-induced resistance and open new opportunities in the fight against multidrug resistance.

Outcomes of surgical management of buschke-lowenstein tumor in a Philippine tertiary hospital.

Buschke-Lowenstein tumor (BLT) is a sexually transmitted infection (STI) caused by the human papillomavirus. This study investigated the profile, management, and outcomes of patients who underwent surgery for BLT from 2015 to 2019 at the Philippine General Hospital. Seven patients underwent surgery for BLT. All were male, with ages ranging from 21 to 41 years. Presenting symptoms were anal mass, foul-smelling discharge, pain, bleeding, and pruritus. All were positive for human immunodeficiency virus. All admitted to having engaged in both insertive and receptive anal intercourse, with multiple partners. All underwent excision with healing by secondary intention. Two had recurrence of warts. Four had an anal stricture. Of these, 3 underwent anal dilatation, while 1 had to undergo proximal bowel diversion. One had intraepithelial carcinoma without dermal invasion on histopathologic analysis. BLT is a rare STI characterized by local aggressiveness but with low malignant potential. Wide excision remains to be the mainstay of treatment.

Neorectum prolapse after rectal cancer surgery corrected with perineal stapled prolapse resection.

A 61-year-old woman developed neorectal prolapse after laparoscopic low anterior resection, total mesorectal excision with partial intersphincteric resection and handsewn coloanal anastomosis for rectal cancer. She presented with a 3 cm full thickness reducible prolapse, with associated anal pain and bleeding. A perineal stapled prolapse resection was performed to address the rectal prolapse, with satisfactory results.

Improved outcomes with implementation of an Enhanced Recovery After Surgery pathway for patients undergoing elective colorectal surgery in the Philippines.

PURPOSE: This study aims to evaluate surgical outcomes (i.e. length of stay [LOS], 30-day morbidity, mortality, reoperation, and readmission rates) with the use of the Enhanced Recovery After Surgery (ERAS) pathway, and determine its association with the rate of compliance to the different ERAS components. METHODS: This was a prospective cohort of patients, who underwent the following elective procedures: stoma reversal (SR), colon resection (CR), and rectal resection (RR). The primary endpoint was to determine the association of compliance to an ERAS pathway and surgical outcomes. These were then retrospectively compared to outcomes prior to the implementation of ERAS. RESULTS: A total of 267 patients were included in the study. The overall compliance to the ERAS component was 92.0% (SR, 91.8%; CR, 93.1%; RR, 90.7%). There was an associated decrease in morbidity rates across all types of surgery, as compliance to ERAS increased. The average total LOS decreased in all groups but was only found to have statistical significance in SR (12.1±6.7 days vs. 10.0±5.4 days, P=0.002) and RR (19.9±11.4 days vs. 16.9±10.5 days, P=0.04) groups. Decreased postoperative LOS was noted in all groups. Morbidity rates were significantly higher after ERAS implementation, but reoperation and mortality rates were found to be similar. CONCLUSION: Increased compliance to ERAS protocol is associated with a decrease in morbidity across all surgery types. The implementation of an ERAS protocol significantly decreased mean hospital LOS, without any increase in major surgical complications. Having your own hospital ERAS pathway improves documentation and accuracy of reporting surgical complications.

McKittrick-Wheelock Syndrome: A Case Series.

McKittrick-Wheelock syndrome is a rare and life-threatening disease characterized by the triad of (1) chronic mucous diarrhea, (2) renal function impairment with hydroelectrolyte imbalance, and (3) a giant colorectal tumor. Often, the tumor is a rectal adenoma. With the mortality being certain, if left untreated, it is important to raise awareness on the presentation, diagnosis, and management of this disease entity. Here, we presented 3 cases of McKittrick-Wheelock syndrome that were successfully managed with surgical resection at the Philippine General Hospital from August 2018 to May 2019. Resolution of their symptoms, reversal of their renal impairment, and correction of their electrolyte depletion were noted after removal of the tumor with a sphincter-saving operation.

Pancreaticoduodenal artery aneurysm associated with polyarteritis nodosa presenting as massive upper gastrointestinal bleeding.

The pancreaticoduodenal arteries are rare sites for true aneurysm formation, but these may develop in association with occlusion of the coeliac circulation, degenerative conditions or inflammatory vascular disorders. These have a high risk of rupture regardless of size or other factors. One identified cause is polyarteritis nodosa (PAN), which is an autoimmune necrotising vascular condition that affects small-sized and medium-sized arteries. We report a case of a 40-year-old man with massive gastrointestinal tract bleeding from a ruptured pancreaticoduodenal artery aneurysm secondary to PAN. This was managed with emergent open aneurysm ligation followed by high-dose corticosteroids and cyclophosphamide pulse therapy. Only three other cases of PAN-associated pancreaticoduodenal artery aneurysms have been reported in the literature.

Modifications to Treatment Plan of Rectal Cancer in Response to COVID-19 at the Philippine General Hospital.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has strained healthcare resources worldwide. Despite the high number of cases, cancer management should remain one of the priorities of healthcare, as any delay would potentially cause disease progression. METHODS: This was an observational study that included nonmetastatic rectal cancer patients managed at the Philippine General Hospital from March 16 to May 31, 2020, coinciding with the lockdown. The treatment received and their outcomes were investigated. RESULTS: Of the 52 patients included, the majority were female (57.7%), belonging to the age group of 50 to 69 years (53.8%), and residing outside the capital (59.6%). On follow-up, 23.1% had no disease progression, 17.3% had local progression, 28.8% had metastatic progression, 19.2% have died, and 11.5% were lost to follow up. The initial plan for 47.6% patients was changed. Of the 21 patients with nonmetastatic disease, 2 underwent outright resection. The remaining 19 required neoadjuvant therapy. Eight have completed their neoadjuvant treatment, 8 are undergoing treatment, 2 had their treatment interrupted, and 1 has yet to begin treatment. Among the 9 patients who completed neoadjuvant therapy, only 1 was able to undergo resection on time. The rest were delayed, with a median time of 4 months. One has repeatedly failed to arrive for her surgery due to public transport limitations. There was 1 adjuvant chemotherapy-related mortality. CONCLUSION: Delays in cancer management resulted in disease progression in several patients. Alternative neoadjuvant treatment options should be considered while taking into account oncologic outcomes, acceptable toxicity, and limitation of potential COVID-19 exposure.

Abdominotransanal resection of a strangulated rectal carcinosarcoma.

This is a case of a 75-year-old man who presented with a 7-month history of a reducible rectal mass. The patient came to the emergency department with a prolapsed necrotic bowel involving a strangulated segment with the rectal mass. He underwent an abdominotransanal resection through a combined abdominal and perineal approach. His postoperative course was unremarkable. Histopathological and immunohistochemical studies showed a rectal carcinosarcoma. Because of a state-mandated lockdown due to the COVID-19 pandemic, the patient failed to follow-up. He was later seen to have metastatic progression. Owing to the poor functional status of the patient, the shared decision of the multidisciplinary team, the patient and his family was to manage him with palliative intent.

Evaluation of MRI Denoising Methods Using Unsupervised Learning.

In this paper we evaluate two unsupervised approaches to denoise Magnetic Resonance Images (MRI) in the complex image space using the raw information that k-space holds. The first method is based on Stein's Unbiased Risk Estimator, while the second approach is based on a blindspot network, which limits the network's receptive field. Both methods are tested on two different datasets, one containing real knee MRI and the other consists of synthetic brain MRI. These datasets contain information about the complex image space which will be used for denoising purposes. Both networks are compared against a state-of-the-art algorithm, Non-Local Means (NLM) using quantitative and qualitative measures. For most given metrics and qualitative measures, both networks outperformed NLM, and they prove to be reliable denoising methods.

Idiopathic megacolon and megarectum in an adult treated with laparoscopic modified Duhamel procedure.

Idiopathic megacolon (IMC) and idiopathic megarectum (IMR) describe an abnormality of the colon or rectum, characterised by a permanent dilatation of the bowel diameter in the absence of an identifiable cause. We present a 23-year-old woman with chronic constipation and excessive straining during defecation who presented at the emergency department in partial gut obstruction with a palpable fecaloma. Manual faecal disimpaction and a sigmoid loop colostomy was initially done. A full thickness rectal biopsy was positive for ganglion cells. Further workup led to the diagnosis of chronic IMC and IMR. The patient underwent laparoscopic modified Duhamel procedure, with an uneventful postoperative course.

Appendiceal intussusception from endometriosis.

An asymptomatic 39-year-old woman was noted to have occult bleeding by faecal immunohistochemical test. Investigations showed a 3 cm×2 cm caecal lesion by colonoscopy that was consistent with abdominal CT scan findings of a 1.6 cm×1.9 cm×2.3 cm enhancing focus in the medial caecal wall. The patient underwent laparoscopic right hemicolectomy after diagnostic laparoscopy and intraoperative colonoscopy revealed an intussuscepted appendix. The final histopathology was an appendiceal intussusception secondary to endometriosis.

EFA6B regulates a stop signal for collective invasion in breast cancer.

Cancer is initiated by somatic mutations in oncogenes or tumor suppressor genes. However, additional alterations provide selective advantages to the tumor cells to resist treatment and develop metastases. Their identification is of paramount importance. Reduced expression of EFA6B (Exchange Factor for ARF6, B) is associated with breast cancer of poor prognosis. Here, we report that loss of EFA6B triggers a transcriptional reprogramming of the cell-to-ECM interaction machinery and unleashes CDC42-dependent collective invasion in collagen. In xenograft experiments, MCF10 DCIS.com cells, a DCIS-to-IDC transition model, invades faster when knocked-out for EFA6B. In addition, invasive and metastatic tumors isolated from patients have lower expression of EFA6B and display gene ontology signatures identical to those of EFA6B knock-out cells. Thus, we reveal an EFA6B-regulated molecular mechanism that controls the invasive potential of mammary cells; this finding opens up avenues for the treatment of invasive breast cancer.